A sub-class of PEPTIDE HYDROLASES that act only near the ends of polypeptide chains.
A subclass of EXOPEPTIDASES that act on the free N terminus end of a polypeptide liberating a single amino acid residue. EC 3.4.11.
A subclass of exopeptidases that includes enzymes which cleave either two or three AMINO ACIDS from the end of a peptide chain.
A lysosomal cysteine proteinase with a specificity similar to that of PAPAIN. The enzyme is present in a variety of tissues and is important in many physiological and pathological processes. In pathology, cathepsin B has been found to be involved in DEMYELINATION; EMPHYSEMA; RHEUMATOID ARTHRITIS, and NEOPLASM INVASIVENESS.
A ZINC-dependent membrane-bound aminopeptidase that catalyzes the N-terminal peptide cleavage of GLUTAMATE (and to a lesser extent ASPARTATE). The enzyme appears to play a role in the catabolic pathway of the RENIN-ANGIOTENSIN SYSTEM.
Enzymes that act at a free C-terminus of a polypeptide to liberate a single amino acid residue.
A zinc containing enzyme of the hydrolase class that catalyzes the removal of the N-terminal amino acid from most L-peptides, particularly those with N-terminal leucine residues but not those with N-terminal lysine or arginine residues. This occurs in tissue cell cytosol, with high activity in the duodenum, liver, and kidney. The activity of this enzyme is commonly assayed using a leucine arylamide chromogenic substrate such as leucyl beta-naphthylamide.
Catalyzes the hydrolysis of pteroylpolyglutamic acids in gamma linkage to pterolylmonoglutamic acid and free glutamic acid. EC 3.4.19.9.
An ubiquitously-expressed lysosomal cysteine protease that is involved in protein processing. The enzyme has both endopeptidase and aminopeptidase activities.
A papain-like cysteine protease that has specificity for amino terminal dipeptides. The enzyme plays a role in the activation of several pro-inflammatory serine proteases by removal of their aminoterminal inhibitory dipeptides. Genetic mutations that cause loss of cathepsin C activity in humans are associated with PAPILLON-LEFEVRE DISEASE.
A serine protease that catalyses the release of an N-terminal dipeptide. Several biologically-active peptides have been identified as dipeptidyl peptidase 4 substrates including INCRETINS; NEUROPEPTIDES; and CHEMOKINES. The protein is also found bound to ADENOSINE DEAMINASE on the T-CELL surface and is believed to play a role in T-cell activation.
A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.
Compounds which inhibit or antagonize biosynthesis or actions of proteases (ENDOPEPTIDASES).
A subclass of PEPTIDE HYDROLASES that catalyze the internal cleavage of PEPTIDES or PROTEINS.
Hydrolases that specifically cleave the peptide bonds found in PROTEINS and PEPTIDES. Examples of sub-subclasses for this group include EXOPEPTIDASES and ENDOPEPTIDASES.
A homologous group of endogenous CYSTEINE PROTEINASE INHIBITORS. The cystatins inhibit most CYSTEINE ENDOPEPTIDASES such as PAPAIN, and other peptidases which have a sulfhydryl group at the active site.
The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.
A group of lysosomal proteinases or endopeptidases found in aqueous extracts of a variety of animal tissues. They function optimally within an acidic pH range. The cathepsins occur as a variety of enzyme subtypes including SERINE PROTEASES; ASPARTIC PROTEINASES; and CYSTEINE PROTEASES.
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.

Quorum sensing-dependent regulation and blockade of exoprotease production in Aeromonas hydrophila. (1/54)

In Aeromonas hydrophila, the ahyI gene encodes a protein responsible for the synthesis of the quorum sensing signal N-butanoyl-L-homoserine lactone (C4-HSL). Inactivation of the ahyI gene on the A. hydrophila chromosome abolishes C4-HSL production. The exoprotease activity of A. hydrophila consists of both serine protease and metalloprotease activities; in the ahyI-negative strain, both are substantially reduced but can be restored by the addition of exogenous C4-HSL. In contrast, mutation of the LuxR homolog AhyR results in the loss of both exoprotease activities, which cannot be restored by exogenous C4-HSL. Furthermore, a substantial reduction in the production of exoprotease by the ahyI+ parent strain is obtained by the addition of N-acylhomoserine lactone analogs that have acyl side chains of 10, 12, or 14 carbons. The inclusion of N-(3-oxododecanoyl)-L-homoserine lactone or N-(3-oxotetradecanoyl)-L-homoserine lactone at 10 microM in overnight cultures of A. hydrophila abolishes exoprotease production in azocasein assays and reduces the activity of all the exoprotease species seen in zymograms.  (+info)

A new 30-kDa ubiquitin-related SUMO-1 hydrolase from bovine brain. (2/54)

SUMO-1 is a ubiquitin-like protein functioning as an important reversible protein modifier. To date there is no report on a SUMO-1 hydrolase/isopeptidase catalyzing the release of SUMO-1 from its precursor or SUMO-1-ligated proteins in mammalian tissues. Here we found multiple activities that cleave the SUMO-1 moiety from two model substrates, (125)I-SUMO-1-alphaNH-HSTVGSMHISPPEPESEEEEEHYC and/or GST-SUMO-1-(35)S-RanGAP1 conjugate, in bovine brain extracts. Of them, a major SUMO-1 C-terminal hydrolase had been partially purified by successive chromatographic operations. The enzyme had the ability to cleave SUMO-1 not only from its precursor but also from a SUMO-1-ligated RanGAP1 but did not exhibit any significant cleavage of the ubiquitin- and NEDD8-precursor. The activity of SUMO-1 hydrolase was almost completely inhibited by N-ethylmaleimide, but not by phenylmethanesulfonyl fluoride, EDTA, and ubiquitin-aldehyde known as a potent inhibitor of deubiquitinylating enzymes. Intriguingly, the apparent molecular mass of the isolated SUMO-1 hydrolase was approximately 30 kDa, which is significantly smaller than the recently identified yeast Smt3/SUMO-1 specific protease Ulp1. These results indicate that there are multiple SUMO-1 hydrolase/isopeptidases in mammalian cells and that the 30-kDa small SUMO-1 hydrolase plays a central role in processing of the SUMO-1-precursor.  (+info)

Global GacA-steered control of cyanide and exoprotease production in Pseudomonas fluorescens involves specific ribosome binding sites. (3/54)

The conserved two-component regulatory system GacS/GacA determines the expression of extracellular products and virulence factors in a variety of Gram-negative bacteria. In the biocontrol strain CHA0 of Pseudomonas fluorescens, the response regulator GacA is essential for the synthesis of extracellular protease (AprA) and secondary metabolites including hydrogen cyanide. GacA was found to exert its control on the hydrogen cyanide biosynthetic genes (hcnABC) and on the aprA gene indirectly via a posttranscriptional mechanism. Expression of a translational hcnA'-'lacZ fusion was GacA-dependent whereas a transcriptional hcnA-lacZ fusion was not. A distinct recognition site overlapping with the ribosome binding site appears to be primordial for GacA-steered regulation. GacA-dependence could be conferred to the Escherichia coli lacZ mRNA by a 3-bp substitution in the ribosome binding site. The gene coding for the global translational repressor RsmA of P. fluorescens was cloned. RsmA overexpression mimicked partial loss of GacA function and involved the same recognition site, suggesting that RsmA is a downstream regulatory element of the GacA control cascade. Mutational inactivation of the chromosomal rsmA gene partially suppressed a gacS defect. Thus, a central, GacA-dependent switch from primary to secondary metabolism may operate at the level of translation.  (+info)

A regulatory RNA (PrrB RNA) modulates expression of secondary metabolite genes in Pseudomonas fluorescens F113. (4/54)

The GacS-GacA two-component signal transduction system, which is highly conserved in gram-negative bacteria, is required for the production of exoenzymes and secondary metabolites in Pseudomonas spp. Screening of a Pseudomonas fluorescens F113 gene bank led to the isolation of a previously undefined locus which could restore secondary metabolite production to both gacS and gacA mutants of F113. Sequence analysis of this locus demonstrated that it did not contain any obvious Pseudomonas protein-coding open reading frames or homologues within available databases. Northern analysis indicated that the locus encodes an RNA (PrrB RNA) which is able to phenotypically complement gacS and gacA mutants and is itself regulated by the GacS-GacA two-component signal transduction system. Primer extension analysis of the 132-base transcript identified the transcription start site located downstream of a sigma(70) promoter sequence from positions -10 to -35. Inactivation of the prrB gene in F113 resulted in a significant reduction of 2, 4-diacetylphloroglucinol (Phl) and hydrogen cyanide (HCN) production, while increased metabolite production was observed when prrB was overexpressed. The prrB gene sequence contains a number of imperfect repeats of the consensus sequence 5'-AGGA-3', and sequence analysis predicted a complex secondary structure featuring multiple putative stem-loops with the consensus sequences predominantly positioned at the single-stranded regions at the ends of the stem-loops. This structure is similar to the CsrB and RsmB regulatory RNAs in Escherichia coli and Erwinia carotovora, respectively. Results suggest that a regulatory RNA molecule is involved in GacA-GacS-mediated regulation of Phl and HCN production in P. fluorescens F113.  (+info)

African swine fever virus protease, a new viral member of the SUMO-1-specific protease family. (5/54)

African swine fever virus (ASFV) is a complex DNA virus that employs polyprotein processing at Gly-Gly-Xaa sites as a strategy to produce several major core components of the viral particle. The virus gene S273R encodes a 31-kDa protein that contains a "core domain" with the conserved catalytic residues characteristic of SUMO-1-specific proteases and the adenovirus protease. Using a COS cell expression system, it was found that protein pS273R is capable of cleaving the viral polyproteins pp62 and pp220 in a specific way giving rise to the same intermediates and mature products as those produced in ASFV-infected cells. Furthermore, protein pS273R, like adenovirus protease and SUMO-1-specific enzymes, is a cysteine protease, because its activity is abolished by mutation of the predicted catalytic histidine and cysteine residues and is inhibited by sulfhydryl-blocking reagents. Protein pS273R is expressed late after infection and is localized in the cytoplasmic viral factories, where it is found associated with virus precursors and mature virions. In the virions, the protein is present in the core shell, a domain where the products of the viral polyproteins are also located. The identification of the ASFV protease will allow a better understanding of the role of polyprotein processing in virus assembly and may contribute to our knowledge of the emerging family of SUMO-1-specific proteases.  (+info)

SmcR-dependent regulation of adaptive phenotypes in Vibrio vulnificus. (6/54)

Vibrio vulnificus contains homologues of the V. harveyi luxR and luxS genes. A null mutation in smcR (luxR) resulted in a defect in starvation survival, inhibition of starvation-induced maintenance of culturability that occurs when V. vulnificus is starved prior to low-temperature incubation, and increased expression of stationary-phase phenotypes.  (+info)

Two-dimensional structure of the native light-harvesting complex LH2 from Rubrivivax gelatinosus and of a truncated form. (7/54)

The light-harvesting complex LH2 of Rubrivivax gelatinosus has an oligomeric structure built from alpha-beta heterodimers containing three bacteriochlorophylls and one carotenoid each. The alpha subunit (71 residues) presents a C-terminal hydrophobic extension (residues 51-71) which is prone to attack by an endogenous protease. This extension can also be cleaved by a mild thermolysin treatment, as demonstrated by electrophoresis and by matrix-assisted laser desorption-time of flight mass spectrometry. This cleavage does not affect the pigment binding sites as shown by absorption spectroscopy. Electron microscopy was used to investigate the structures of the native and thermolysin cleaved forms of the complexes. Two-dimensional crystals of the reconstituted complexes were examined after negative staining and cryomicroscopy. Projection maps at 10 A resolution were calculated, demonstrating the nonameric ring-like organization of alpha-beta subunits. The cleaved form presents the same structural features. We conclude that the LH2 complex is structurally homologous to the Rhodopseudomonas acidophila LH2. The hydrophobic C-terminal extension does not fold back in the membrane, but lays out on the periplasmic surface of the complex.  (+info)

A second quorum-sensing system regulates cell surface properties but not phenazine antibiotic production in Pseudomonas aureofaciens. (8/54)

The root-associated biological control bacterium Pseudomonas aureofaciens 30-84 produces a range of exoproducts, including protease and phenazines. Phenazine antibiotic biosynthesis by phzXYFABCD is regulated in part by the PhzR-PhzI quorum-sensing system. Mutants defective in phzR or phzI produce very low levels of phenazines but wild-type levels of exoprotease. In the present study, a second genomic region of strain 30-84 was identified that, when present in trans, increased beta-galactosidase activity in a genomic phzB::lacZ reporter and partially restored phenazine production to a phzR mutant. Sequence analysis identified two adjacent genes, csaR and csaI, that encode members of the LuxR-LuxI family of regulatory proteins. No putative promoter region is present upstream of the csaI start codon and no lux box-like element was found in either the csaR promoter or the 30-bp intergenic region between csaR and csaI. Both the PhzR-PhzI and CsaR-CsaI systems are regulated by the GacS-GacA two-component regulatory system. In contrast to the multicopy effects of csaR and csaI in trans, a genomic csaR mutant (30-84R2) and a csaI mutant (30-84I2) did not exhibit altered phenazine production in vitro or in situ, indicating that the CsaR-CsaI system is not involved in phenazine regulation in strain 30-84. Both mutants also produced wild-type levels of protease. However, disruption of both csaI and phzI or both csaR and phzR eliminated both phenazine and protease production completely. Thus, the two quorum-sensing systems do not interact for phenazine regulation but do interact for protease regulation. Additionally, the CsaI N-acylhomoserine lactone (AHL) signal was not recognized by the phenazine AHL reporter 30-84I/Z but was recognized by the AHL reporters Chromobacterium violaceum CV026 and Agrobacterium tumefaciens A136(pCF240). Inactivation of csaR resulted in a smooth mucoid colony phenotype and formation of cell aggregates in broth, suggesting that CsaR is involved in regulating biosynthesis of cell surface components. Strain 30-84I/I2 exhibited mucoid colony and clumping phenotypes similar to those of 30-84R2. Both phenotypes were reversed by complementation with csaR-csaI or by the addition of the CsaI AHL signal. Both quorum-sensing systems play a role in colonization by strain 30-84. Whereas loss of PhzR resulted in a 6.6-fold decrease in colonization by strain 30-84 on wheat roots in natural soil, a phzR csaR double mutant resulted in a 47-fold decrease. These data suggest that gene(s) regulated by the CsaR-CsaI system also plays a role in the rhizosphere competence of P. aureofaciens 30-84.  (+info)

Exopeptidases are a type of enzyme that break down peptides or proteins by cleaving off one amino acid at a time from the end of the protein or peptide chain. There are two main types of exopeptidases: aminopeptidases, which remove amino acids from the N-terminus (the end of the chain with a free amino group), and carboxypeptidases, which remove amino acids from the C-terminus (the end of the chain with a free carboxyl group).

Exopeptidases play important roles in various biological processes, including protein degradation and turnover, digestion, and processing of peptide hormones and neuropeptides. They are also involved in the pathogenesis of certain diseases, such as cancer and neurodegenerative disorders, where they can contribute to the accumulation of abnormal proteins and toxic protein fragments.

Exopeptidases are found in various organisms, including bacteria, fungi, plants, and animals. They are also used in biotechnology and research, for example, in the production of pharmaceuticals, food ingredients, and diagnostic tools.

Aminopeptidases are a group of enzymes that catalyze the removal of amino acids from the N-terminus of polypeptides and proteins. They play important roles in various biological processes, including protein degradation, processing, and activation. Aminopeptidases are classified based on their specificity for different types of amino acids and the mechanism of their action. Some of the well-known aminopeptidases include leucine aminopeptidase, alanyl aminopeptidase, and arginine aminopeptidase. They are widely distributed in nature and found in various tissues and organisms, including bacteria, plants, and animals. In humans, aminopeptidases are involved in several physiological functions, such as digestion, immune response, and blood pressure regulation.

Dipeptidyl-peptidases (DPPs) and tripeptidyl-peptidases (TPPs) are two types of enzymes that belong to the class of peptidases, which are proteins that help break down other proteins into smaller peptides or individual amino acids.

Dipeptidyl-peptidases cleave dipeptides (two-amino acid units) from the N-terminus (the end with a free amino group) of polypeptides and proteins, while tripeptidyl-peptidases cleave tripeptides (three-amino acid units) from the same location.

There are several different isoforms of DPPs and TPPs that have been identified in various organisms, including humans. These enzymes play important roles in regulating various physiological processes, such as digestion, immune function, and blood glucose homeostasis.

Inhibitors of DPP-4, one specific isoform of DPPs, have been developed for the treatment of type 2 diabetes, as they help increase the levels of incretin hormones that stimulate insulin secretion and suppress glucagon production.

Cathepsin B is a lysosomal cysteine protease that plays a role in various physiological processes, including intracellular protein degradation, antigen presentation, and extracellular matrix remodeling. It is produced as an inactive precursor (procathepsin B) and activated upon cleavage of the propeptide by other proteases or autocatalytically. Cathepsin B has a wide range of substrates, including collagen, elastin, and various intracellular proteins. Its dysregulation has been implicated in several pathological conditions, such as cancer, neurodegenerative diseases, and inflammatory disorders.

Glutamyl Aminopeptidase (GAP, or sometimes also abbreviated as GP) is an enzyme that is found in many tissues throughout the body, including the kidneys and the intestines. Its primary function is to help break down proteins into smaller peptides and individual amino acids by removing certain types of amino acids from the ends of these protein chains.

GAP is a type of exopeptidase enzyme, which means that it works on the outside edges of proteins rather than in the middle. Specifically, GAP removes the amino acid glutamic acid (or its amide form, glutamine) from the N-terminus (the beginning end) of peptides and proteins.

In clinical settings, GAP is often measured in blood or urine samples as a biomarker for various medical conditions. For example, elevated levels of GAP in the blood may indicate liver disease or kidney damage, while decreased levels may be associated with certain types of cancer or gastrointestinal disorders. However, it's important to note that GAP is just one of many factors that doctors may consider when diagnosing and treating these conditions.

Carboxypeptidases are a group of enzymes that catalyze the cleavage of peptide bonds at the carboxyl-terminal end of polypeptides or proteins. They specifically remove the last amino acid residue from the protein chain, provided that it has a free carboxyl group and is not blocked by another chemical group. Carboxypeptidases are classified into two main types based on their catalytic mechanism: serine carboxypeptidases and metallo-carboxypeptidases.

Serine carboxypeptidases, also known as chymotrypsin C or carboxypeptidase C, use a serine residue in their active site to catalyze the hydrolysis of peptide bonds. They are found in various organisms, including animals and bacteria.

Metallo-carboxypeptidases, on the other hand, require a metal ion (usually zinc) for their catalytic activity. They can be further divided into several subtypes based on their structure and substrate specificity. For example, carboxypeptidase A prefers to cleave hydrophobic amino acids from the carboxyl-terminal end of proteins, while carboxypeptidase B specifically removes basic residues (lysine or arginine).

Carboxypeptidases have important roles in various biological processes, such as protein maturation, digestion, and regulation of blood pressure. Dysregulation of these enzymes has been implicated in several diseases, including cancer, neurodegenerative disorders, and cardiovascular disease.

Leucyl aminopeptidase (LAP) is an enzyme that plays a role in the metabolism and breakdown of proteins. It is found in various tissues and organs throughout the body, including the small intestine, liver, and kidneys. LAP specifically catalyzes the removal of leucine, a type of amino acid, from the N-terminus (the beginning) of peptides and proteins. This enzyme is important for the proper digestion and absorption of dietary proteins, as well as for the regulation of various physiological processes in the body. Abnormal levels or activity of LAP have been implicated in certain diseases, such as cancer and liver disease.

Gamma-glutamyl hydrolase (GGH) is an enzyme that plays a role in the metabolism of certain amino acids, specifically glutathione and its related compounds. Glutathione is a tripeptide consisting of cysteine, glutamic acid, and glycine, and it functions as an important antioxidant in the body.

GGH catalyzes the hydrolysis of the gamma-glutamyl bond in glutathione and its related compounds, releasing free glutamate and a dipeptide. This reaction is an essential step in the recycling of these amino acids and the synthesis of new glutathione molecules.

A deficiency in GGH activity has been associated with several diseases, including neurodegenerative disorders and cancer. Inhibitors of GGH have also been investigated as potential therapeutic agents for the treatment of certain cancers, as they may help to reduce the levels of glutathione and enhance the effectiveness of chemotherapy drugs.

Cathepsin H is a lysosomal cysteine protease that plays a role in intracellular protein degradation and turnover. It is expressed in various tissues, including the spleen, thymus, lungs, and immune cells. Cathepsin H has been implicated in several physiological processes, such as antigen presentation, bone resorption, and extracellular matrix remodeling. Additionally, its dysregulation has been associated with various pathological conditions, including cancer, neurodegenerative disorders, and infectious diseases.

The enzyme's active site contains a catalytic triad composed of cysteine, histidine, and aspartic acid residues, which facilitates the proteolytic activity. Cathepsin H exhibits specificity for peptide bonds containing hydrophobic or aromatic amino acids, making it an important player in processing and degrading various cellular proteins.

In summary, Cathepsin H is a lysosomal cysteine protease involved in protein turnover and degradation with potential implications in several pathological conditions when dysregulated.

Cathepsin C is a lysosomal cysteine protease that plays a role in intracellular protein degradation and activation of other proteases. It is also known as dipeptidyl peptidase I (DPP I) because of its ability to remove dipeptides from the N-terminus of polypeptides. Cathepsin C is widely expressed in many tissues, including immune cells, and has been implicated in various physiological and pathological processes such as antigen presentation, bone resorption, and tumor cell invasion. Defects in the gene encoding cathepsin C have been associated with several genetic disorders, including Papillon-Lefèvre syndrome and Haim-Munk syndrome, which are characterized by severe periodontal disease and skin abnormalities.

Dipeptidyl peptidase 4 (DPP-4) is a serine protease enzyme that is widely distributed in various tissues and organs, including the kidney, liver, intestines, and immune cells. It plays a crucial role in regulating several biological processes, such as glucose metabolism, immune function, and cell signaling.

In terms of glucose metabolism, DPP-4 is responsible for breaking down incretin hormones, including glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), which are released from the gut in response to food intake. These hormones stimulate insulin secretion from pancreatic beta cells, suppress glucagon release, and promote satiety, thereby helping to regulate blood sugar levels. By degrading GLP-1 and GIP, DPP-4 reduces their activity and contributes to the development of type 2 diabetes.

DPP-4 inhibitors are a class of drugs used to treat type 2 diabetes by blocking the action of DPP-4 and increasing incretin hormone levels, leading to improved insulin secretion and glucose control.

Substrate specificity in the context of medical biochemistry and enzymology refers to the ability of an enzyme to selectively bind and catalyze a chemical reaction with a particular substrate (or a group of similar substrates) while discriminating against other molecules that are not substrates. This specificity arises from the three-dimensional structure of the enzyme, which has evolved to match the shape, charge distribution, and functional groups of its physiological substrate(s).

Substrate specificity is a fundamental property of enzymes that enables them to carry out highly selective chemical transformations in the complex cellular environment. The active site of an enzyme, where the catalysis takes place, has a unique conformation that complements the shape and charge distribution of its substrate(s). This ensures efficient recognition, binding, and conversion of the substrate into the desired product while minimizing unwanted side reactions with other molecules.

Substrate specificity can be categorized as:

1. Absolute specificity: An enzyme that can only act on a single substrate or a very narrow group of structurally related substrates, showing no activity towards any other molecule.
2. Group specificity: An enzyme that prefers to act on a particular functional group or class of compounds but can still accommodate minor structural variations within the substrate.
3. Broad or promiscuous specificity: An enzyme that can act on a wide range of structurally diverse substrates, albeit with varying catalytic efficiencies.

Understanding substrate specificity is crucial for elucidating enzymatic mechanisms, designing drugs that target specific enzymes or pathways, and developing biotechnological applications that rely on the controlled manipulation of enzyme activities.

Protease inhibitors are a class of antiviral drugs that are used to treat infections caused by retroviruses, such as the human immunodeficiency virus (HIV), which is responsible for causing AIDS. These drugs work by blocking the activity of protease enzymes, which are necessary for the replication and multiplication of the virus within infected cells.

Protease enzymes play a crucial role in the life cycle of retroviruses by cleaving viral polyproteins into functional units that are required for the assembly of new viral particles. By inhibiting the activity of these enzymes, protease inhibitors prevent the virus from replicating and spreading to other cells, thereby slowing down the progression of the infection.

Protease inhibitors are often used in combination with other antiretroviral drugs as part of highly active antiretroviral therapy (HAART) for the treatment of HIV/AIDS. Common examples of protease inhibitors include saquinavir, ritonavir, indinavir, and atazanavir. While these drugs have been successful in improving the outcomes of people living with HIV/AIDS, they can also cause side effects such as nausea, diarrhea, headaches, and lipodystrophy (changes in body fat distribution).

Endopeptidases are a type of enzyme that breaks down proteins by cleaving peptide bonds inside the polypeptide chain. They are also known as proteinases or endoproteinases. These enzymes work within the interior of the protein molecule, cutting it at specific points along its length, as opposed to exopeptidases, which remove individual amino acids from the ends of the protein chain.

Endopeptidases play a crucial role in various biological processes, such as digestion, blood coagulation, and programmed cell death (apoptosis). They are classified based on their catalytic mechanism and the structure of their active site. Some examples of endopeptidase families include serine proteases, cysteine proteases, aspartic proteases, and metalloproteases.

It is important to note that while endopeptidases are essential for normal physiological functions, they can also contribute to disease processes when their activity is unregulated or misdirected. For instance, excessive endopeptidase activity has been implicated in the pathogenesis of neurodegenerative disorders, cancer, and inflammatory conditions.

Peptide hydrolases, also known as proteases or peptidases, are a group of enzymes that catalyze the hydrolysis of peptide bonds in proteins and peptides. They play a crucial role in various biological processes such as protein degradation, digestion, cell signaling, and regulation of various physiological functions. Based on their catalytic mechanism and the specificity for the peptide bond, they are classified into several types, including serine proteases, cysteine proteases, aspartic proteases, and metalloproteases. These enzymes have important clinical applications in the diagnosis and treatment of various diseases, such as cancer, viral infections, and inflammatory disorders.

Cystatins are a group of proteins that inhibit cysteine proteases, which are enzymes that break down other proteins. Cystatins are found in various biological fluids and tissues, including tears, saliva, seminal plasma, and urine. They play an important role in regulating protein catabolism and protecting cells from excessive protease activity. There are three main types of cystatins: type 1 (cystatin C), type 2 (cystatin M, cystatin N, and fetuin), and type 3 (kininogens). Abnormal levels of cystatins have been associated with various pathological conditions, such as cancer, neurodegenerative diseases, and inflammatory disorders.

An amino acid sequence is the specific order of amino acids in a protein or peptide molecule, formed by the linking of the amino group (-NH2) of one amino acid to the carboxyl group (-COOH) of another amino acid through a peptide bond. The sequence is determined by the genetic code and is unique to each type of protein or peptide. It plays a crucial role in determining the three-dimensional structure and function of proteins.

Cathepsins are a type of proteolytic enzymes, which are found in lysosomes and are responsible for breaking down proteins inside the cell. They are classified as papain-like cysteine proteases and play important roles in various physiological processes, including tissue remodeling, antigen presentation, and apoptosis (programmed cell death). There are several different types of cathepsins, including cathepsin B, C, D, F, H, K, L, S, V, and X/Z, each with distinct substrate specificities and functions.

Dysregulation of cathepsins has been implicated in various pathological conditions, such as cancer, neurodegenerative diseases, and inflammatory disorders. For example, overexpression or hyperactivation of certain cathepsins has been shown to contribute to tumor invasion and metastasis, while their inhibition has been explored as a potential therapeutic strategy in cancer treatment. Similarly, abnormal levels of cathepsins have been linked to the progression of neurodegenerative diseases like Alzheimer's and Parkinson's, making them attractive targets for drug development.

Molecular sequence data refers to the specific arrangement of molecules, most commonly nucleotides in DNA or RNA, or amino acids in proteins, that make up a biological macromolecule. This data is generated through laboratory techniques such as sequencing, and provides information about the exact order of the constituent molecules. This data is crucial in various fields of biology, including genetics, evolution, and molecular biology, allowing for comparisons between different organisms, identification of genetic variations, and studies of gene function and regulation.

An exopeptidase is any peptidase that catalyzes the cleavage of the terminal (or the penultimate) peptide bond; the process ... Some examples of exopeptidases include: Carboxypeptidase A - cleaves C-terminal Phe, Tyr, Trp, or Leu Carboxypeptidase B - ... an exopeptidase is further classified as an aminopeptidase or a carboxypeptidase, respectively. Thus, an aminopeptidase, an ... C-terminal Pro from dipeptides The Proteolysis Map Endopeptidase Edman degradation Dansyl chloride Protease Exopeptidases at ...
An exopeptidase inhibitor is a drug that inhibits one or more exopeptidase enzymes. Exopeptidases are one of two types of ... Exopeptidases cleave peptide bonds of terminal amino acids, resulting in the release of a single amino acid or dipeptide from ... Endopeptidase inhibitor Tao, L; Zhou, H; Guo, XS; Long, RJ; Zhu, Y; Cheng, W (August 2011). "Contribution of exopeptidases to ... Various enkephalinase inhibitors, such as ketalorphan, spinorphin, and tynorphin, are mainly exopeptidase inhibitors. ...
McDonald JK, Schwabe C (1977). "Intracellular exopeptidases". In Barrett AJ (ed.). Proteinases in Mammalian Cells and Tissues. ...
McDonald, J.K.; Schwabe, C. (1977). "Intracellular exopeptidases". In Barrett, A.J. (ed.). Proteinases in Mammalian Cells and ...
Walter R, Simmons WH, Yoshimoto T (April 1980). "Proline specific endo- and exopeptidases". Molecular and Cellular Biochemistry ...
Exopeptidases-Advances in Research and Application: 2012 Edition. ScholarlyEditions. ISBN 978-1-4816-0415-4. Serkina, A. V.; ...
... s are exopeptidases, classified under EC number 3.4.13. Membrane dipeptidase Dipeptidases at the U.S. National ...
Exopeptidases are enzymes that can cleave the end of an amino acid side chain mostly through the addition of water. ... Exopeptidase enzymes exist in the small intestine. These enzymes have two classes: aminopeptidases are a brush border enzyme ...
... the exopeptidase, angiotensin converting enzyme 2 (ACE2). However, it was later discovered that neutralization of ACE2 by ...
... is a monomeric pancreatic exopeptidase. It is involved in zymogen inhibition. GRCh38: Ensembl release 89: ...
There are two subgroups of metalloproteinases: Exopeptidases, metalloexopeptidases (EC number: 3.4.17). Endopeptidases, ...
The species secretes more than 20 different proteases, including exopeptidases and endopeptidases. These proteases allow T. ...
The enzyme acts as an exopeptidase to activate neuropeptides. It does that by cleaving off basic C-terminal amino acids, ...
1998). "Dipeptidyl peptidase III is a zinc metallo-exopeptidase. Molecular cloning and expression". Biochem. J. 329 ( Pt 2) (Pt ...
Aminopeptidases function as exopeptidases which remove amino acids from the amino-terminus of proteins. Aminopeptidase N (CD13/ ...
Some detach the terminal amino acids from the protein chain (exopeptidases, such as aminopeptidases, carboxypeptidase A); ...
A metalloexopeptidase is a type of enzyme that acts as a metalloproteinase exopeptidase. These enzymes have a catalytic ...
The enzymes involved are proteinases (cathepsins - B, D, H & L, and calpains) and exopeptidases (peptidase and aminopeptidase ...
It is an exopeptidase with strict carboxypeptidase activity, while most other cathepsins are endopeptidases. Cathepsin Z has an ...
Various exopeptidase which further digests polypeptides into amino acids complete the digestion of proteins.[citation needed] ...
... s at the U.S. National Library of Medicine Medical Subject Headings (MeSH) Exopeptidase The Proteolysis Map Portal ... For this reason, endopeptidases cannot break down peptides into monomers, while exopeptidases can break down proteins into ... in contrast to exopeptidases, which break peptide bonds from end-pieces of terminal amino acids. ...
... exopeptidases. Some viral papain-like proteases, including those of coronaviruses, can also cleave isopeptide bonds and can ...
This extra sequence is not necessary if exopeptidases are used to remove N-terminal His-tags (e.g., Qiagen TAGZyme). ... Furthermore, exopeptidase cleavage may solve the unspecific cleavage observed when using endoprotease-based tag removal. ...
The vast majority of the family are endopeptidases, although there is an exopeptidase, tripeptidyl peptidase. Structures have ...
... an exopeptidase) Alatriopril - also inhibits ACE Daglutril - also inhibits endothelin converting enzyme (ECE) (an exopeptidase ... whereas exopeptidases break terminal bonds, resulting in the release of a single amino acid or dipeptide from the peptide chain ... the other being exopeptidases. Endopeptidases cleave peptide bonds of non-terminal amino acids (that is, they cut proteins/ ... an exopeptidase) Sampatrilat Spinorphan - also inhibits APN, ACE, and DPP-3 Tynorphin - also inhibits APN, ACE, and DPP-3 ...
It is often grouped under exopeptidases, proteases that work only on the outermost peptide bonds of a polypeptide chain. The ...
... exopeptidases). They are widely distributed throughout the animal and plant kingdoms and are found in many subcellular ...
Some of these enzymes include: Various exopeptidases and endopeptidases including dipeptidase and aminopeptidases that convert ...
... is a carboxy terminal specific exopeptidase, meaning it catalyzes the cleavage of the carboxy terminal peptide ...
DPP-4 is a serine exopeptidase that cleaves X-proline or X-alanine dipeptides from the N-terminus of polypeptides. Peptide ...
An exopeptidase is any peptidase that catalyzes the cleavage of the terminal (or the penultimate) peptide bond; the process ... Some examples of exopeptidases include: Carboxypeptidase A - cleaves C-terminal Phe, Tyr, Trp, or Leu Carboxypeptidase B - ... an exopeptidase is further classified as an aminopeptidase or a carboxypeptidase, respectively. Thus, an aminopeptidase, an ... C-terminal Pro from dipeptides The Proteolysis Map Endopeptidase Edman degradation Dansyl chloride Protease Exopeptidases at ...
Glucocorticoids mobilize macrophages by transcriptionally up-regulating the exopeptidase DPP4 David Diaz-Jimenez 1 , Maria ... Glucocorticoids mobilize macrophages by transcriptionally up-regulating the exopeptidase DPP4 David Diaz-Jimenez et al. J Biol ... Among glucocorticoid-regulated genes, we identified the exopeptidase dipeptidyl peptidase-4 (DPP4) as a critical glucocorticoid ...
Exopeptidase Carboxypeptidase B1‡ 6978697. [135]. Others Pancreatic lipase† 1865646. [136]. Pancreatic lipase-related protein 1 ...
EXOPEPTIDASES EXOPEPTIDASES EXOPEPTIDASAS FAMÍLIA DE PAIS SOLTEIROS SINGLE-PARENT FAMILY FAMILIA DE PADRES SOLTEROS ...
Glucocorticoids mobilize macrophages by transcriptionally up-regulating the exopeptidase DPP4. J Biol Chem; doi: 10.1074/jbc. ... Glucocorticoids mobilize macrophages by transcriptionally up-regulating the exopeptidase DPP4. J Biol Chem; doi: 10.1074/jbc. ...
GCPII has been shown to both indirectly and directly increase the concentration of glutamate in the extracellular space.[29] GCPII directly cleaves NAAG into NAA and glutamate.[3][4] NAAG has been shown, in high concentration, to indirectly inhibit the release of neutrotransmitters, such as GABA and glutamate. It does this through interaction with and activation of presynaptic group II mGluRs.[29] Thus, in the presence of NAAG peptidase, the concentration of NAAG is kept in check, and glutamate and GABA, among other neurotransmitters, are not inhibited. Researchers have been able to show that effective and selective GCPII inhibitors are able to decrease the brains levels of glutamate and even provide protection from apoptosis or degradation of brain neurons in many animal models of stroke, amyotrophic lateral sclerosis, and neuropathic pain.[4] This inhibition of these NAAG peptidases, sometimes referred to as NPs, are thought to provide this protection from apoptosis or degradation of brain ...
As ziconotide is a peptide, it is expected to be completely degraded by endopeptidases and exopeptidases (Phase I hydrolytic ... Ziconotide is cleaved by endopeptidases and exopeptidases at multiple sites on the peptide. Following passage from the CSF into ...
As ziconotide is a peptide, it is expected to be completely degraded by endopeptidases and exopeptidases (Phase I hydrolytic ... Ziconotide is cleaved by endopeptidases and exopeptidases at multiple sites on the peptide. Following passage from the CSF into ...
Superfamily c.56.5: Zn-dependent exopeptidases [53187] (5 families) *. Family c.56.5.4: Bacterial exopeptidases [53204] (2 ...
Lundgren, S. et al., Yeast beta-Alanine Synthase Shares a Structural Scaffold and Origin with Dizinc-dependent Exopeptidases. J ...
Zn-catalyzed tert-butyl nicotinate-directed amide cleavage as a biomimic of metallo-exopeptidase activity. C. C. D. Wybon, C. ...
9. Peptides generated ex vivo from serum proteins by tumor-specific exopeptidases are not useful biomarkers in ovarian cancer. ...
Glucocorticoids mobilize macrophages by transcriptionally up-regulating the exopeptidase DPP4. Diaz-Jimenez D, Petrillo MG, ...
The pancreatic enzymes, including endopeptidases (trypsin, chymotrypsin and elastase), exopeptidases (carboxypeptidase A and B ... The exposure of these AAs can act as substrates to be further digested by exopeptidases (Carboxypeptidase A and B), which may ...
IGNITOR contains a scientifically crafted combination of endopeptidases and exopeptidases which belong to a class of enzymes ... Endopeptidases hydrolyze protein molecules at the interior peptide bonds, liberating smaller peptides, while exopeptidases ...
... by endopeptidases and exopeptidases. These enzymes create small tripeptide fragments of three amino acid sequences for optimal ...
Further, CD26 is an intrinsic membrane glycoprotein and a serine exopeptidase that cleaves X-proline dipeptides from the N- ...
Dipeptidyl Peptidase-4 (DPP-4) is a membrane serine exopeptidase that cleaves proline dipeptides form the N-terminal end of ...
Skoric-Milosavljevic, D., Tadros, R., Bosada, F. M., Tessadori, F., van Weerd, J. H., Woudstra, O. I., Tjong, F. V. Y., Lahrouchi, N., Bajolle, F., Cordell, H. J., Agopian, A. J., Blue, G. M., Barge-Schaapveld, D. Q., Gewillig, M. H., Preuss, C., Lodder, E. M., Barnett, P., Ilgun, A., Beekman, L., van Duijvenboden, K., & 60 anderenBokenkamp, R., Müller-Nurasyid, M., Vliegen, H. W., Konings, T. C., van Melle, J. P., van Dijk, A., van Kimmenade, R. R., Roos-Hesselink, J. W., Sieswerda, G., Meijboom, F., Abdul-Khaliq, H., Berger, F., Dittrich, S., Hitz, M-P., Moosmann, J., Riede, F-T., Schubert, S., Galan, P., Lathrop, G. M., Munter, H. M., Al-Chalabi, A., Shaw, C. E., Shaw, P. J., Morrison, K. E., Veldink, J. H., van den Berg, L. H., Evans, S. M., Nobrega, M. A., Aneas, I., Radivojkov-Blagojevic, M., Meitinger, T., Oechslin, E., Mondal, T., Bergin, M. L., Smythe, J. F., Altamirano-Diaz, L., Lougheed, J., Bouma, B. J., Chaix, M. A., Kline, J., Bassett, A. S., Andelfinger, G., van der Palen, R. L., ...
2000; EXOPROTEASES (now EXOPEPTIDASES) was indexed under PEPTIDE HYDROLASES 1977-1999. History Note:. 2000; use EXOPEPTIDASES ( ... Exopeptidases - Preferred Concept UI. M0079942. Scope note. A sub-class of PEPTIDE HYDROLASES that act only near the ends of ...
2000; EXOPROTEASES (now EXOPEPTIDASES) was indexed under PEPTIDE HYDROLASES 1977-1999. History Note. 2000; use EXOPEPTIDASES ( ... Exopeptidases Preferred Concept UI. M0079942. Registry Number. EC 3.4.-. Scope Note. A sub-class of PEPTIDE HYDROLASES that act ... Exopeptidases Preferred Term Term UI T109945. Date10/12/1999. LexicalTag NON. ThesaurusID NLM (2000). ... Exopeptidase Term UI T109944. Date10/12/1999. LexicalTag NON. ThesaurusID NLM (2000). ...
2000; EXOPROTEASES (now EXOPEPTIDASES) was indexed under PEPTIDE HYDROLASES 1977-1999. History Note. 2000; use EXOPEPTIDASES ( ... Exopeptidases Preferred Concept UI. M0079942. Registry Number. EC 3.4.-. Scope Note. A sub-class of PEPTIDE HYDROLASES that act ... Exopeptidases Preferred Term Term UI T109945. Date10/12/1999. LexicalTag NON. ThesaurusID NLM (2000). ... Exopeptidase Term UI T109944. Date10/12/1999. LexicalTag NON. ThesaurusID NLM (2000). ...
Metallo-carboxypeptidases (MCPs) are exopeptidases, which contain a zinc atom in the active site, involved in the hydrolysis of ...
The acylaminoacyl peptidase from Aeropyrum pernix K1 thought to be an exopeptidase displays endopeptidase activity. [http://www ...
... an omega exopeptidase which cleaves pyroglutamic acid from the N-terminus of peptides and proteins. Three classes of ...
It is an intrinsic membrane glycoprotein and a serine exopeptidase that cleaves X-proline dipeptides from the N-terminus of ...
Nardi: Serum trypsin (or arginine exopeptidase) screening test for cancer of the pancreas Gastroenterology 38 50-51 1.1960 ...
  • Some examples of exopeptidases include: Carboxypeptidase A - cleaves C-terminal Phe, Tyr, Trp, or Leu Carboxypeptidase B - cleaves C-terminal Lys or Arg Aminopeptidase - cleaves any N-terminal amino acid Prolinase - cleaves N-terminal Pro from dipeptides Prolidase - cleaves C-terminal Pro from dipeptides The Proteolysis Map Endopeptidase Edman degradation Dansyl chloride Protease Exopeptidases at the U.S. National Library of Medicine Medical Subject Headings (MeSH) Škárka, Bohumil (1992). (wikipedia.org)
  • Flavorpro 937MDP is an exopeptidase preparation with low levels of endopeptidase activity. (dairyfoods.com)
  • DG Protect includes both endopeptidase and exopeptidase activity chosen for their ability to hydrolyze gluten proteins, as well as a unique mixture of protease enzymes and lactase to assist the digestion of multiple constituents of dairy products. (nutrirestore.com)
  • Specifically, enzymatic action creates the correct endopeptidase cleavage pattern near the long chain amino acids that need to be hydrolyzed by the exopeptidase, producing rapid degradation of gluten. (nutrirestore.com)
  • Can act as both an exopeptidase and endopeptidase. (lu.se)
  • Cellular receptor ACE2, serine protease TMPRSS2 and exopeptidase CD26 (also known as DPP4) are the three membrane bound proteins potentially implicated in SARS-CoV-2 infection. (ias.ac.in)
  • The unique combination of endopeptidases and exopeptidases present in DG Protect efficiently degrade both the internal and terminal peptides bonds of the gluten molecule. (nutrirestore.com)
  • To complete the digestive process to produce single amino acids from a protein chain, an exopeptidase is needed. (allthescience.org)
  • Where the amino acid is joined to the rest of the peptide chain and which amino acids are joined together plays a role in determining which exopeptidase will break the bond. (allthescience.org)
  • Other exopeptidases, called dipeptidases, break apart particular pairs of amino acids. (allthescience.org)
  • Some of them can detach the terminal amino acids from the protein chain (exopeptidases, such as aminopeptidases, carboxypeptidase A), while others attack internal peptide bonds of a protein (endopeptidases, such as trypsin, chymotrypsin, pepsin, papain and elastase). (stratech.co.uk)
  • Exopeptidase treatment can release terminal amino acids from peptides, which in turn may contribute to formation of volatile compounds by Maillard reactions. (ku.dk)
  • Exopeptidases, such as Flavorpro 937MDP can be used to control bitterness by removing these bitter-tasting peptides. (dairyfoods.com)
  • Sequence analysis revealed that these peptides were generated by 'cancer-type'-specific exopeptidase activities. (selectbiosciences.com)
  • Depending on whether the amino acid is released from the amino or the carboxy terminal (N-terminus or C-terminus), an exopeptidase is further classified as an aminopeptidase or a carboxypeptidase, respectively. (wikipedia.org)
  • Carboxypeptidase is an exopeptidase that breaks the bond between the second last and the last amino acid at the C terminal end. (allthescience.org)
  • Another exopeptidase, aminopeptidase, carries out the same action but at the N terminal end. (allthescience.org)
  • proteins by endopeptidases, exopeptidases and membrane-bound dipeptidases. (aqa.org.uk)
  • Exopeptidases are one group of enzymes involved in the complete digestion of proteins. (allthescience.org)
  • On the other hand, exopeptidases are able to degrade proteins into monomers. (herbs2000.com)
  • It is just the opposite of exopeptidases that split peptide bonds from the terminal amino acid end pieces. (herbs2000.com)
  • The presence of this loop, which allows the enzyme to function as an exopeptidase, thus complicates the inhibition mechanism, rendering cathepsin B much less susceptible than other cysteine. (lu.se)
  • There are several different exopeptidases, each of which has a highly specific mode of action. (allthescience.org)
  • IGNITOR contains a scientifically crafted combination of endopeptidases and exopeptidases which belong to a class of enzymes called aminopeptidases. (ventrian.com)
  • Endopeptidases hydrolyze protein molecules at the interior peptide bonds, liberating smaller peptides, while exopeptidases hydrolyze the protein molecule at the terminus of the peptide chain, releasing individual amino acids. (ventrian.com)
  • Examples of sub-subclasses for this group include EXOPEPTIDASES and ENDOPEPTIDASES . (lookformedical.com)
  • Further, CD26 is an intrinsic membrane glycoprotein and a serine exopeptidase that cleaves X-proline dipeptides from the N-terminus of polypeptides. (thermofisher.com)
  • Dipeptidyl Peptidase-4 (DPP-4) is a membrane serine exopeptidase that cleaves proline dipeptides form the N-terminal end of protein substrates. (proteopedia.org)
  • Some examples of exopeptidases include: Carboxypeptidase A - cleaves C-terminal Phe, Tyr, Trp, or Leu Carboxypeptidase B - cleaves C-terminal Lys or Arg Aminopeptidase - cleaves any N-terminal amino acid Prolinase - cleaves N-terminal Pro from dipeptides Prolidase - cleaves C-terminal Pro from dipeptides The Proteolysis Map Endopeptidase Edman degradation Dansyl chloride Protease Exopeptidases at the U.S. National Library of Medicine Medical Subject Headings (MeSH) Škárka, Bohumil (1992). (wikipedia.org)
  • This thesis investigates the kinetic and stability characteristics of recombinant human brain pyroglutamyl peptidase PAPI, an omega exopeptidase which cleaves pyroglutamic acid from the N-terminus of peptides and proteins. (dcu.ie)
  • They include a wide range of peptidase activity, including exopeptidase, endopeptidase, oligopeptidase and omega-peptidase activity. (embl.de)
  • Descriptive term for proteolytic enzymes, both endopeptideases and exopeptidases. (wordquests.info)
  • The immobilized porcine pancreatic exopeptidases and its application in casein hydrolysates debittering. (bsu.by)
  • Carboxypeptidase B is a recombinant exopeptidase which catalyzes the hydrolysis of the amino acids lysine, arginine and ornithine from C-terminal end of polypeptides. (asa-enzyme.de)
  • Exopeptidases and their application to reduce bitterness in food: a review. (bsu.by)