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Search The CSA
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Catalytic Site Atlas

CSA LITERATURE entry for 1hja

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

Literature Report

IntroductionAlpha-Chymotrypsin is a proteolytic enzyme of the well-studied serine protease family with the Ser His Asp catalytic triad with a charge-relay mechanism of protein hydrolysis.
MechansimHydrolytic proteolysis by alpha-chymotrypsin begins with initial nucleophilic attack on the peptide bond by Ser 195, activated by deprotonation by His 57. This leads to the formation of a tetrahedral intermediate, stabilised by the amide groups of Ser 195 and Gly 193. Subsequent collapse of this intermediate, assisted by protonation of the leaving group by His 57 and Asp 102 leads to an acyl enzyme intermediate. Activation of a water molecule by His 57 and Asp 102 facilitates hydrolysis of this intermediate, resulting in the reformation of the catalytically active serine residue and the release of the product facilitated by protonation with His 57.
Reaction

Catalytic Sites for 1hja

Annotated By Reference To The Literature - Site 1 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
SerC195195macie:sideChainActs as the nucleophile in attack of the substrate and formation of the acyl-enzyme intermediate; also stabilises the tetrahedral transition states by formation of the oxyanion hole through the backbone amide group.
SerC195195macie:mainChainAmideActs as the nucleophile in attack of the substrate and formation of the acyl-enzyme intermediate; also stabilises the tetrahedral transition states by formation of the oxyanion hole through the backbone amide group.
GlyC193193macie:mainChainAmideForms part of the oxyanion hole to stabilise the tetrahedral intermediate and transition states.
AspB102102macie:sideChainActivates His 57.
HisB5757macie:sideChainActivates Ser 195 by general base catalysis and facilitates collapse of the intermediate by general acid catalysis. Also activates a water molecule by general base catalysis and allows release of the products by general acid catalysis.

Annotated By Reference To The Literature - Site 2 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
SerC195195macie:sideChainActs as the nucleophile in attack of the substrate and formation of the acyl-enzyme intermediate; also stabilises the tetrahedral transition states by formation of the oxyanion hole through the backbone amide group.
SerC195195macie:mainChainAmideActs as the nucleophile in attack of the substrate and formation of the acyl-enzyme intermediate; also stabilises the tetrahedral transition states by formation of the oxyanion hole through the backbone amide group.
GlyC193193macie:mainChainAmideForms part of the oxyanion hole to stabilise the tetrahedral intermediate and transition states.
AspB102102macie:sideChainActivates His 57.
HisB5757macie:sideChainActivates Ser 195 by general base catalysis and facilitates collapse of the intermediate by general acid catalysis. Also activates a water molecule by general base catalysis and allows release of the products by general acid catalysis.

Literature References

Notes:
Brothers HM 2nd
Catalytic activity of the serine proteases alpha-chymotrypsin and alpha-lytic protease tagged at the active site with a (terpyridine)platinum(II) chromophore.
Biochemistry 1990 29 7468-7474
PubMed: 2223778
Wells GB
Structure at the active site of an acylenzyme of alpha-chymotrypsin and implications for the catalytic mechanism. An electron nuclear double resonance study.
J Biol Chem 1994 269 4577-4586
PubMed: 8308029
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