Chymotrypsin - wikipedia Chymotrypsin Chymotrypsin Crystallographic structure of Bos taurus chymotrypsinogen. Identifiers EC number 3.4. 21.1 CAS number 9004 - 07 - 3 Databases IntEnz IntEnz view BRENDA BRENDA entry ExPASy NiceZyme view KEGG KEGG entry MetaCyc metabolic pathway PRIAM profile PDB structures RCSB PDB PDBe PDBsum Gene Ontology AmiGO / QuickGO Search PMC articles PubMed articles NCBI proteins Chymotrypsin C Identifiers EC number 3.4. 21.2 CAS number 9036 - 09 - 3 Databases IntEnz IntEnz view BRENDA BRENDA entry ExPASy NiceZyme view KEGG KEGG entry MetaCyc metabolic pathway PRIAM profile PDB structures RCSB PDB PDBe PDBsum Search PMC articles PubMed articles NCBI proteins Chymotrypsin ( EC 3.4. 21.1, chymotrypsins A and B, alpha - chymar ophth, avazyme, chymar, chymotest, enzeon, quimar, quimotrase, alpha - chymar, alpha - chymotrypsin A, alpha - chymotrypsin ) is a digestive enzyme component of pancreatic juice acting in the duodenum where it performs proteolysis, the breakdown of proteins and polypeptides. Chymotrypsin preferentially cleaves peptide amide bonds where the side - chain of the amino acid N - terminal to the scissile amide bond ( the P position ) is a large hydrophobic amino acid ( tyrosine, tryptophan, and phenylalanine ). These amino acids contain an aromatic ring in their sidechain that fits into a ' hydrophobic pocket ' ( the S position ) of the enzyme. It is activated in the presence of trypsin. The hydrophobic and shape complementarity between the peptide substrate P sidechain and the enzyme S binding cavity accounts for the substrate specificity of this enzyme. Chymotrypsin also hydrolyzes other amide bonds in peptides at slower rates, particularly those containing leucine and methionine at the P position. Structurally, it is the archetypal structure for its superfamily, the PA clan of proteases. Contents 1 Activation 2 Mechanism of action and kinetics 3 Isozymes 4 See also 5 References 6 Further reading 7 External links Activation Chymotrypsin is synthesized in the pancreas by protein biosynthesis as a precursor called chymotrypsinogen that is enzymatically inactive. Trypsin activates chymotrypsinogen by cleaving peptidic bonds in positions Arg15 - Ile16 and produces π - Chymotrypsin. In turn, aminic group ( - NH3 ) of the Ile16 residue interacts with the side chain of Glu194, producing the `` oxyanion hole '' and the hydrophobic `` S1 pocket ''. Moreover, Chymotrypsin induces its own activation by cleaving in positions 14 - 15, 146 - 147 and 148 - 149, producing α - Chymotrypsin ( which is more active and stable than π - Chymotrypsin ). The resulting molecule is a three - polypeptide molecule interconnected via disulfide bonds. Mechanism of action and kinetics See also : Catalytic triad In vivo, chymotrypsin is a proteolytic enzyme ( Serine protease ) acting in the digestive systems of many organisms. It facilitates the cleavage of peptide bonds by a hydrolysis reaction, which despite being thermodynamically favorable occurs extremely slowly in the absence of a catalyst. The main substrates of chymotrypsin are peptide bonds in which the amino acid N - terminal to the bond is a tryptophan, tyrosine, phenylalanine, or leucine. Like many proteases, chymotrypsin will also hydrolyse amide bonds in vitro, a virtue that enabled the use of substrate analogs such as N - acetyl - L - phenylalanine p - nitrophenyl amide for enzyme assays. Mechanism of peptide bond cleavage in α - chymotrypsin Chymotrypsin cleaves peptide bonds by attacking the unreactive carbonyl group with a powerful nucleophile, the serine 195 residue located in the active site of the enzyme, which briefly becomes covalently bonded to the substrate, forming an enzyme - substrate intermediate. Along with histidine 57 and aspartic acid 102, this serine residue constitutes the catalytic triad of the active site. These findings rely on inhibition assays and the study of the kinetics of cleavage of the aforementioned substrate, exploiting the fact that the enzyme - substrate intermediate p - nitrophenolate has a yellow colour, enabling us to measure its concentration by measuring light absorbance at 410 nm. It was found that the reaction of chymotrypsin with its substrate takes place in two stages, an initial `` burst '' phase at the beginning of the reaction and a steady - state phase following Michaelis - Menten kinetics. The mode of action of chymotrypsin explains this as hydrolysis takes place in two steps. First acylation of the substrate to form an acyl - enzyme intermediate and then deacylation in order to return the enzyme to its original state. This occurs via the concerted action of the three amino acid residues in the catalytic triad. Aspartate hydrogen bonds to the N - δ hydrogen of histidine, increasing the pKa of its ε nitrogen and thus making it able to deprotonate serine. It is this deprotonation that allows the serine side chain to act as a nucleophile and bind to the electron - deficient carbonyl carbon of the protein main chain. Ionization of the carbonyl oxygen is stabilized by formation of two hydrogen bonds to adjacent main chain N - hydrogens. This occurs in the oxyanion hole. This forms a tetrahedral adduct and breakage of the peptide bond. An acyl - enzyme intermediate, bound to the serine, is formed, and the newly formed amino terminus of the cleaved protein can dissociate. In the second reaction step, a water molecule is activated by the basic histidine, and acts as a nucleophile. The oxygen of water attacks the carbonyl carbon of the serine - bound acyl group, resulting in formation of a second tetrahedral adduct, regeneration of the serine - OH group, and release of a proton, as well as the protein fragment with the newly formed carboxyl terminus Isozymes Chymotrypsinogen B1 Identifiers Symbol CTRB1 Entrez 1504 HUGO 2521 OMIM 118890 RefSeq NM_001906 UniProt P17538 Other data EC number 3.4. 21.1 Locus Chr. 16 q23. 1 Chymotrypsinogen B2 Identifiers Symbol CTRB2 Entrez 440387 HUGO 2522 RefSeq NM_001025200 UniProt Q6GPI1 Other data EC number 3.4. 21.1 Locus Chr. 16 q22. 3 Chymotrypsin C ( caldecrin ) Identifiers Symbol CTRC Entrez 11330 HUGO 2523 OMIM 601405 RefSeq NM_007272 UniProt Q99895 Other data EC number 3.4. 21.2 Locus Chr. 1 p36. 21 See also Trypsin PA clan of proteases References Jump up ^ PDB : 1CHG ​ ; Freer ST, Kraut J, Robertus JD, Wright HT, Xuong NH ( April 1970 ). `` Chymotrypsinogen : 2.5 - angstrom crystal structure, comparison with alpha - chymotrypsin, and implications for zymogen activation ''. Biochemistry. 9 ( 9 ) : 1997 -- 2009. doi : 10.1021 / bi00811a022. PMID 5442169. Jump up ^ Wilcox PE ( 1970 ). `` Chymotrypsinogens -- chymotrypsins ''. Methods in Enzymology. Methods in Enzymology. 19 : 64 -- 108. doi : 10.1016 / 0076 - 6879 ( 70 ) 19007 - 0. ISBN 978 - 0 - 12 - 181881 - 4. Jump up ^ Appel W ( December 1986 ). `` Chymotrypsin : molecular and catalytic properties ''. Clin. Biochem. 19 ( 6 ) : 317 -- 22. doi : 10.1016 / S0009 - 9120 ( 86 ) 80002 - 9. PMID 3555886. Jump up ^ Berger A, Schechter I ( February 1970 ). `` Mapping the active site of papain with the aid of peptide substrates and inhibitors ''. Philos. Trans. R. Soc. Lond. B Biol. Sci. 257 ( 813 ) : 249 -- 64. doi : 10.1098 / rstb. 1970.0024. PMID 4399049. ^ Jump up to : Petsko, Gregory ; Ringe, Dagmar ( 2009 ). Protein Structure and Function. Oxford : Oxford University Press. pp. 78 -- 79. ISBN 978 - 0 - 19 - 955684 - 7. Further reading Stryer L, Berg JM, Tymoczko JL ( 2002 ). Biochemistry. San Francisco : W.H. Freeman. ISBN 0 - 7167 - 4684 - 0. Grisham CM, Reginald H ( 2005 ). Biochemistry. Australia : Thomson Brooks / Cole. ISBN 0 - 534 - 49033 - 6. External links The MEROPS online database for peptidases and their inhibitors : S01. 001 Chymotrypsin at the US National Library of Medicine Medical Subject Headings ( MeSH ) Endopeptidases : serine proteases / serine endopeptidases ( EC 3.4. 21 ) Digestive enzymes Enteropeptidase Trypsin Chymotrypsin Elastase Neutrophil Pancreatic Coagulation factors : Thrombin Factor VIIa Factor IXa Factor Xa Factor XIa Factor XIIa Kallikrein PSA KLK1 KLK2 KLK3 KLK4 KLK5 KLK6 KLK7 KLK8 KLK9 KLK10 KLK11 KLK12 KLK13 KLK14 KLK15 fibrinolysis : Plasmin Plasminogen activator Tissue plasminogen activator Urinary plasminogen activator Complement system Factor B Factor D Factor I MASP MASP1 MASP2 C3 - convertase Other immune system Chymase Granzyme Tryptase Proteinase 3 / Myeloblastin Venombin Ancrod Batroxobin Other Acrosin Prolyl endopeptidase Pronase Proprotein convertases Prostasin Reelin Subtilisin / Furin Streptokinase S1P Cathepsin Enzymes Activity Active site Binding site Catalytic triad Oxyanion hole Enzyme promiscuity Catalytically perfect enzyme Coenzyme Cofactor Enzyme catalysis Regulation Allosteric regulation Cooperativity Enzyme inhibitor Classification EC number Enzyme superfamily Enzyme family List of enzymes Kinetics Enzyme kinetics Eadie -- Hofstee diagram Hanes -- Woolf plot Lineweaver -- Burk plot Michaelis -- Menten kinetics Types EC1 Oxidoreductases ( list ) EC2 Transferases ( list ) EC3 Hydrolases ( list ) EC4 Lyases ( list ) EC5 Isomerases ( list ) EC6 Ligases ( list ) Molecular and Cellular Biology portal Retrieved from `` https://en.wikipedia.org/w/index.php?title=Chymotrypsin&oldid=816189295 '' Categories : Genes on human chromosome 16 Genes on human chromosome 1 EC 3.4. 21 Peptidase Hidden categories : All articles with unsourced statements Articles with unsourced statements from July 2017 Protein pages needing a picture Talk Search Contents About Wikipedia Català Čeština Deutsch Eesti Español فارسی Français Galego Հայերեն Italiano עברית ಕನ್ನಡ 日本 語 Norsk Polski Português Српски / srpski Srpskohrvatski / српскохрватски Suomi Svenska 中文 Edit links This page was last edited on 19 December 2017, at 21 : 07. 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Question: where does cleavage of the peptide bond by chymotrypsin occur
Answer: where the side-chain of the amino acid N-terminal to the scissile amide bond (the P1 position) is a large hydrophobic amino acid (tyrosine, tryptophan, and phenylalanine); digestive systems; positions 14-15, 146-147 and 148-149