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Catalytic Site Atlas Version 2.2.12
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CSA entry for 1ca0
Original Entry
Title:
Complex (serine protease/inhibitor)
Compound:
Bovine chymotrypsin
Mutant:
No
UniProt/Swiss-Prot:
P00766-CTRA_BOVIN
P05067-A4_HUMAN
EC Class:
3.4.21.1
Other CSA Entries:
Overview of all sites for 1ca0
Homologues of 1ca0
Entries for UniProt/Swiss-Prot: P00766
Entries for UniProt/Swiss-Prot: P05067
Entries for EC: 3.4.21.1
Other Databases:
PDB entry: 1ca0
PDBsum entry: 1ca0
UniProt/Swiss-Prot: P00766
UniProt/Swiss-Prot: P05067
IntEnz entry: 3.4.21.1
Literature Report:
Introduction:
Chymotrypsin is one of the well known serine proteases found in the human digestive system, and is able to catalyse the breakdown of peptide substrates to amino acids, showing a preference for cleavage after aromatic residues such as phenylalanine. The enzyme shares significant sequence and structural homology to many mammalian serine proteases, including trypsin and elastase, as well as being part of a wider family involving proteases from diverse organisms including bacteria.
Mechanism:
The general mechanism for chymotrypsin is the classic serine protease mechanism. The peptide bond of the substrate is attacked by the nucleophilic Ser 195 residue, which is able to act as a nucleophile due to the acid-base action of the His 57 Asp 102 diad. This forms a tetrahedral intermediate stabilised by contacts with the amide portions of Ser 195 and Gly 196. Collapse of the tetrahedral intermediate, facilitated by protonation of the leaving group by His 57 leads to an acyl enzyme intermediate. Activation of a water molecule by the His-Asp diad allows hydrolysis of this intermediate so that the products are released and the catalytic Ser residue regenerated.
Sites:

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Found by:
Literature reference 
PsiBLAST alignment on 1hja
PsiBLAST alignment on 1n8o

ResidueChainNumberUniProt numberFunctional part FunctionTargetDescription
HISB 57 57Sidechain
Acid/baseSubstrate
Acid/baseResidue
Acid/baseWater
Acts as general acid base in several stages of the reaction. First, deprotonates Ser 195 to allow it to act as a a nucleophile. Second, protonates the leaving group to allow collapse of the tetrahedral intermediate. Third, activates water molecule to facilitate hydrolysis of the acyl-enzyme intermediate.
Evidence from paper Evidence concerns Evidence type
PubMed ID 1583684 Current protein Structural similarity to homologue of known mechanism

ResidueChainNumberUniProt numberFunctional part FunctionTargetDescription
ASPB 102 102Sidechain
ElectrostaticResidue
Acts to modify the pKa of His 57 to allow it to act as a general acid base at physiological pH.
Evidence from paper Evidence concerns Evidence type
PubMed ID 1583684 Current protein Structural similarity to homologue of known mechanism

ResidueChainNumberUniProt numberFunctional part FunctionTargetDescription
SERC 195 195Sidechain, Backbone amide
ElectrostaticTransition state
NucleophileSubstrate
Acts as nucleophile to attack the peptide bond and form the tetrahedral intermediate which collapses to give the products. Also acts to stabilise this intermediate through the amide portion of its backbone which forms part of the oxyanion hole.
Evidence from paper Evidence concerns Evidence type
PubMed ID 1583684 Current protein Structural similarity to homologue of known mechanism

ResidueChainNumberUniProt numberFunctional part FunctionTargetDescription
GLYC 196 196Backbone amide
ElectrostaticTransition state
Acts to stabilise the tetrahedral intermediate through electrostatic interactions between its amide and the oxyanion.
Evidence from paper Evidence concerns Evidence type
PubMed ID 1583684 Current protein Structural similarity to homologue of known mechanism
Notes:
Relative exists where catalytic residues are all on one chain.
References:
1
Crystal and molecular structure of the bovine alpha-chymotrypsin-eglin c complex at 2.0 A resolution.
F. Frigerio and A. Coda and L. Pugliese and C. Lionetti and E. Menegatti and G. Amiconi and H. P. Schnebli and P. Ascenzi and M. Bolognesi
J Mol Biol 225, (1) 107-23, (1992).
1583684
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