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Catalytic Site Atlas Version 2.2.12
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Swiss-Prot code:
EC number:
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CSA entry for 1hja
Original Entry
Title:
Complex (hydrolase/inhibitor)
Compound:
Alpha-chymotrypsin
Mutant:
No
UniProt/Swiss-Prot:
P00766-CTRA_BOVIN
P00767-CTRB_BOVIN
P01004-IOVO_MELGA
EC Class:
3.4.21.1
Other CSA Entries:
Overview of all sites for 1hja
Homologues of 1hja
Entries for UniProt/Swiss-Prot: P00766
Entries for UniProt/Swiss-Prot: P00767
Entries for UniProt/Swiss-Prot: P01004
Entries for EC: 3.4.21.1
Other Databases:
PDB entry: 1hja
PDBsum entry: 1hja
UniProt/Swiss-Prot: P00766
UniProt/Swiss-Prot: P00767
UniProt/Swiss-Prot: P01004
IntEnz entry: 3.4.21.1
Literature Report:
Introduction:
Alpha-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.
Mechanism:
Hydrolytic 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.
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Found by:
Literature reference 

ResidueChainNumberUniProt numberFunctional part FunctionTargetDescription
HISB 57 57Sidechain
Acid/baseResidue
Acid/baseSubstrate
Activates 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.
Evidence from paper Evidence concerns Evidence type
PubMed ID 8308029 Current protein Computer modelling
PubMed ID 2223778 Current protein pH dependence of reaction
PubMed ID 8308029 Current protein Residue is positioned appropriately (ligand position known)
PubMed ID 2223778 Current protein Structural similarity to homologue of known mechanism
PubMed ID 2223778 Current protein Mutagenesis of residue
PubMed ID 8308029 Current protein Residue is covalently bound to intermediate, based on structural data
PubMed ID 2223778 Current protein Chemical modification of residue
PubMed ID 2223778 Current protein Computer modelling

ResidueChainNumberUniProt numberFunctional part FunctionTargetDescription
ASPB 102 102Sidechain
ElectrostaticResidue
Activates His 57.
Evidence from paper Evidence concerns Evidence type
PubMed ID 2223778 Current protein Structural similarity to homologue of known mechanism
PubMed ID 2223778 Current protein Computer modelling

ResidueChainNumberUniProt numberFunctional part FunctionTargetDescription
GLYC 193 193Backbone amide
ElectrostaticTransition state
Forms part of the oxyanion hole to stabilise the tetrahedral intermediate and transition states.
Evidence from paper Evidence concerns Evidence type
PubMed ID 8308029 Current protein Residue is positioned appropriately (ligand position known)
PubMed ID 8308029 Current protein Computer modelling
PubMed ID 2223778 Current protein Structural similarity to homologue of known mechanism

ResidueChainNumberUniProt numberFunctional part FunctionTargetDescription
SERC 195 195Sidechain, Backbone amide
ElectrostaticTransition state
NucleophileSubstrate
Acts 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.
Evidence from paper Evidence concerns Evidence type
PubMed ID 8308029 Current protein Residue is positioned appropriately (ligand position known)
PubMed ID 2223778 Current protein Structural similarity to homologue of known mechanism
PubMed ID 8308029 Current protein Computer modelling
References:
1
Catalytic activity of the serine proteases alpha-chymotrypsin and alpha-lytic protease tagged at the active site with a (terpyridine)platinum(II) chromophore.
H. M. Brothers and N. M. Kostić
Biochemistry 29, (32) 7468-74, (1990).
2223778
2
Structure at the active site of an acylenzyme of alpha-chymotrypsin and implications for the catalytic mechanism. An electron nuclear double resonance study.
G. B. Wells and D. Mustafi and M. W. Makinen
J Biol Chem 269, (6) 4577-86, (1994).
8308029
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