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Search The CSA
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Catalytic Site Atlas

CSA LITERATURE entry for 1hfs

E.C. namestromelysin 1
SpeciesHomo sapiens (Human)
E.C. Number (IntEnz) 3.4.24.17
CSA Homologues of 1hfsThere are 160 Homologs
CSA Entries With UniProtID P08254
CSA Entries With EC Number 3.4.24.17
PDBe Entry 1hfs
PDBSum Entry 1hfs
MACiE Entry 1hfs

Literature Report

IntroductionHuman stromelysin-1 (MMP-3) is one of the most attractive targets in drug discovery today because of its broad physiological specificity.This extracellular endopeptidase of vertebrate tissues degrades various proteoglycan components of the extracellular matrix as well as fibronectin and laminin. Stromelysin also plays a unique role among the MMPs because of its involvement in activation of other MMP proenzymes.
MechansimThe general base role is assigned to the Glu202 in MMPs. The water molecule, coordinated to the metal in the reactant complex, is being extremely polarised between the glutamate base and zinc Lewis acid in the Glu- H2 O- Zn bridge.Upon substrate delivery, the water oxygen performs a nucleophilic attack on the peptide carbon.Concertedly, the glutamate abstracts the proton from the water and shuttles it toward the nitrogen of the scissile amide. The tetrahedral gem -diolate intermediate is formed, bidentatelycoordinated to the metal. According to the classic proposals for zinc endopeptidases, the final breakdown of the C- N bond occurs only after the second proton transferd from the water oxygen, mediated again by the conserved glutamate; the oxyanion hole here is poentially stabilised by His231.
Reaction

Catalytic Sites for 1hfs

Annotated By Reference To The Literature - Site 1 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
GluA202219macie:sideChainActs as a general base on water, to create nucleophile from attack on the amide carbonyl.

Literature References

Notes:His231 has not been confirmed to be catalytic.
Pelmenschikov V
Catalytic mechanism of matrix metalloproteinases: two-layered ONIOM study.
Inorg Chem 2002 41 5659-5666
PubMed: 12401069
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