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Catalytic Site Atlas

CSA LITERATURE entry for 1n8o

E.C. namechymotrypsin
SpeciesBos taurus (Bovine)
E.C. Number (IntEnz) 3.4.21.1
CSA Homologues of 1n8oThere are 1290 Homologs
CSA Entries With UniProtID P00766
CSA Entries With EC Number 3.4.21.1
PDBe Entry 1n8o
PDBSum Entry 1n8o
MACiE Entry 1n8o

Literature Report

IntroductionChymotrypsin 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.
MechansimThe 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.
Reaction

Catalytic Sites for 1n8o

Annotated By Reference To The Literature - Site 2 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
SerC195195macie:sideChainActs as nucleophile to attack the peptide bond, forming the tetrahedral intermediate which collapses to give the products. Stabilises the tetrahedral intermediate through electrostatic contacts between its amide group and the oxyanion.
SerC195195macie:mainChainAmideActs as nucleophile to attack the peptide bond, forming the tetrahedral intermediate which collapses to give the products. Stabilises the tetrahedral intermediate through electrostatic contacts between its amide group and the oxyanion.
GlyC196196macie:mainChainAmideForms electrostatic interactions with the oxyanion to stabilise the tetrahedral intermediate.
AspB102102macie:sideChainModifies the pKa of His 57 to allow it to act as a general acid base at physiological pH.
HisB5757macie:sideChainActs as general acid base in several stages of the reaction. First, enables Ser 195 to act as a nucleophile by deprotonating it. Second, protonates the leaving group to allow collapse of the tetrahedral intermediate. Third deprotonates a water molecule to allow it to act as a nucleophile and hydrolyse the acyl enzyme intermediate.

Literature References

Notes:Relative exists where catalytic residues are all on one chain.
Frigerio F
Crystal and molecular structure of the bovine alpha-chymotrypsin-eglin c complex at 2.0 A resolution.
J Mol Biol 1992 225 107-123
PubMed: 1583684
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