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Search The CSA
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Catalytic Site Atlas

CSA LITERATURE entry for 1a0j

E.C. nametrypsin
SpeciesSalmo salar (Atlantic salmon)
E.C. Number (IntEnz) 3.4.21.4
CSA Homologues of 1a0jThere are 1232 Homologs
CSA Entries With UniProtID P35033
CSA Entries With EC Number 3.4.21.4
PDBe Entry 1a0j
PDBSum Entry 1a0j
MACiE Entry 1a0j

Literature Report

IntroductionThe mechanism of the serine proteases is commonly believed to be among the best understood of all enzymes. As their name suggests, they are involved in hydrolysis of proteins using a serine nucleophile. As well as the active site, there is also a 'specificity pocket' which determines which amino acids the enzyme will cleave at. For trypsin, this pocket contains a negatively charged residue, which results in it having a preference for cleaving at positively charged residues i.e. lysine or arginine.
MechansimThe key feature of the mechanism is the presence of the catalytic triad of serine, histidine and aspartate. Serine, having been deprotonated by histidine, attacks the carbonyl of the substrate. The negatively charged tetrahedral intermediate is stabilised by the oxyanion hole, while the positive charge on histidine is stabilised by the aspartate residue. When the tetrahedral intermediate collapses, the amide bond of the substrate is broken. The acylenzyme intermediate is hydrolysed by a water molecule, activated by histidine, to release the product and restore the enzyme to its active state.

Catalytic Sites for 1a0j

Annotated By Reference To The Literature - Site 1 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
SerA195192macie:sideChainWhen activated by His57, Ser195 is the nucleophile which attacks the substrate carbonyl. The backbone NH also forms part of the oxyanion hole which polarises the substrate carbonyl to facilitate attack and then stabilises the negatively charged oxygen in the transition state.
SerA195192macie:mainChainAmideWhen activated by His57, Ser195 is the nucleophile which attacks the substrate carbonyl. The backbone NH also forms part of the oxyanion hole which polarises the substrate carbonyl to facilitate attack and then stabilises the negatively charged oxygen in the transition state.
HisA5755macie:sideChainForms part of the catalytic triad. Deprotonates Ser195 to activate it as a nucleophile, and is stabilised by hydrogen bonding interactions with Asp102. In the deacylation step, deprotonates a water molecule to activate it as a nucleophile.
AspA10299macie:sideChainForms part of the catalytic triad. Stabilises the positive charge on His57.
GlyA193190macie:mainChainAmideForms part of the oxyanion hole which polarises the substrate carbonyl to facilitate attack and then stabilises the negatively charged oxygen in the transition state.

Literature References

Notes:
Topf M
Molecular dynamics simulations of the acyl-enzyme and the tetrahedral intermediate in the deacylation step of serine proteases.
Proteins 2002 47 357-369
PubMed: 11948789
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