Chymotrypsin: Difference between revisions
wiki for Sequence of proteases - chymotrypsin A - trypsin - elastase, (histidine 57, aspartic acid 102, serine 195)(at 3-D ACTIVE site) |
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'''Chymotrypsin''' is a digestive [[enzyme]] that can perform [[proteolysis]].<ref name="Wilcox_1970">{{ cite journal | author = Wilcox PE | year = 1970 | title = Chymotrypsinogens — chymotrypsins | journal = Methods in Enzymology | volume = 19 | pages = 64–108 | doi = 10.1016/0076-6879(70)19007-0}}</ref> Chymotrypsin preferentially cleaves peptide amide bonds where the carboxyl side of amide bond (the |
'''Chymotrypsin''' is a digestive [[enzyme]] that can perform [[proteolysis]].<ref name="Wilcox_1970">{{ cite journal | author = Wilcox PE | year = 1970 | title = Chymotrypsinogens — chymotrypsins | journal = Methods in Enzymology | volume = 19 | pages = 64–108 | doi = 10.1016/0076-6879(70)19007-0}}</ref> Chymotrypsin preferentially cleaves peptide amide bonds where the carboxyl side of amide bond (the P<sub>1</sub> position) is a [[tyrosine]], [[tryptophan]], or [[phenylalanine]]. These [[amino acid]]s contain an [[aromatic]] ring in their [[substituent|sidechain]] that fits into a '[[hydrophobe|hydrophobic]] pocket' (the S<sub>1</sub> position) of the enzyme. The hydrophobic and shape complementarity between the peptide [[enzyme substrate|substrate]] S<sub>1</sub> sidechain and the enzyme P<sub>1</sub> binding cavity accounts for the substrate specificity of this enzyme.<ref name="pmid3555886">{{cite journal | author = Appel W | title = Chymotrypsin: molecular and catalytic properties | journal = Clin. Biochem. | volume = 19 | issue = 6 | pages = 317–22 | year = 1986 | month = December | pmid = 3555886 | doi = 10.1016/S0009-9120(86)80002-9| url = | issn = }}</ref> Chymotrypsin also hydrolyzes other amide bonds in peptides at slower rates, particularly those containing [[leucine]] at the S<sub>1</sub> position. |
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==Activation of chymotrypsin== |
==Activation of chymotrypsin== |
Revision as of 09:55, 12 June 2010
chymotrypsin | |||||||||
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Identifiers | |||||||||
EC no. | 3.4.21.1 | ||||||||
CAS no. | 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 | ||||||||
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chymotrypsin C | |||||||||
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Identifiers | |||||||||
EC no. | 3.4.21.2 | ||||||||
CAS no. | 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 | ||||||||
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Template:FixBunching Chymotrypsin is a digestive enzyme that can perform proteolysis.[1] Chymotrypsin preferentially cleaves peptide amide bonds where the carboxyl side of amide bond (the P1 position) is a tyrosine, tryptophan, or phenylalanine. These amino acids contain an aromatic ring in their sidechain that fits into a 'hydrophobic pocket' (the S1 position) of the enzyme. The hydrophobic and shape complementarity between the peptide substrate S1 sidechain and the enzyme P1 binding cavity accounts for the substrate specificity of this enzyme.[2] Chymotrypsin also hydrolyzes other amide bonds in peptides at slower rates, particularly those containing leucine at the S1 position.
Activation of chymotrypsin
Chymotrypsin is synthesized in the pancreas by protein biosynthesis as a precursor called chymotrypsinogen that is enzymatically inactive. On cleavage by trypsin into two parts that are still connected via an S-S bond, cleaved chymotrypsinogen molecules can activate each other by removing two small peptides in a trans-proteolysis. The resulting molecule is active chymotrypsin, a three-polypeptide molecule interconnected via disulfide bonds.
Action and kinetics of chymotrypsin
In vivo, chymotrypsin is a proteolytic enzyme acting in the digestive systems of mammals and other organisms. It facilitates the cleavage of peptide bonds by a hydrolysis reaction, a process that, albeit thermodynamically favourable, occurs extremely slowly in the absence of a catalyst. The main substrates of chymotrypsin include tryptophan, tyrosine, phenylalanine, leucine, and methionine, which are cleaved at the carboxyl terminal. 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.
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.
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. It is also called "ping-pong" mechanism. 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.
Isozymes
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References
- ^ Wilcox PE (1970). "Chymotrypsinogens — chymotrypsins". Methods in Enzymology. 19: 64–108. doi:10.1016/0076-6879(70)19007-0.
- ^ Appel W (1986). "Chymotrypsin: molecular and catalytic properties". Clin. Biochem. 19 (6): 317–22. doi:10.1016/S0009-9120(86)80002-9. PMID 3555886.
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Further reading
- Stryer L, Berg JM, Tymoczko JL (2002). Biochemistry. San Francisco: W.H. Freeman. ISBN 0-7167-4684-0.
{{cite book}}
: CS1 maint: multiple names: authors list (link) - Grisham CM, Reginald H (2005). Biochemistry. Australia: Thomson Brooks/Cole. ISBN 0-534-49033-6.
External links
- Chymotrypsin at the U.S. National Library of Medicine Medical Subject Headings (MeSH)