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Search The CSA
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Catalytic Site Atlas

CSA LITERATURE entry for 1itq

E.C. namemembrane dipeptidase
SpeciesHomo sapiens (Human)
E.C. Number (IntEnz) 3.4.13.19
CSA Homologues of 1itq
CSA Entries With UniProtID P16444
CSA Entries With EC Number 3.4.13.19
PDBe Entry 1itq
PDBSum Entry 1itq
MACiE Entry M0168

Literature Report

IntroductionHuman Renal Dipeptidase (hrDP), sourced from Homo sapiens, is a membrane-bound glyco-protein involved in hydrolysis of dipeptides. Hydrophobic dipeptides are cleaved preferentially, including prolyl amino acids. In the renal cortex, it is bound to the microvillar membranes in the brush-border region of proximal tubules. hrDP is involved in the hydrolytic metabolism of penem and carbapenem beta-lactam antibiotics. It also plays important roles in the renal metabolism of glutathione.
MechansimAsp 288 deprotonates a water molecule in the active site. The activated water molecule performs nucleophilic attack upon the carbonyl group of the amide. An oxyanion tetrahedral transition state is formed. This is stabilised electrostatically by protonated His 152. The tetrahedral transition state then collapses and the amine group of the scissile amide bond leaves.

Catalytic Sites for 1itq

Annotated By Reference To The Literature - Site 1 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
HisA152168macie:sideChainProtonated His 152 electrostatically stabilises the oxyanion tetrahedral transition state.
AspA288304macie:sideChainAsp 288 activates a water molecule in the active site by deprotonation.

Annotated By Reference To The Literature - Site 2 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
HisB152168macie:sideChainProtonated His 152 electrostatically stabilises the oxyanion tetrahedral transition state.
AspB288304macie:sideChainAsp 288 activates a water molecule in the active site by deprotonation.

Literature References

Notes:
Nitanai Y
Crystal structure of human renal dipeptidase involved in beta-lactam hydrolysis.
J Mol Biol 2002 321 177-184
PubMed: 12144777
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