Structural and functional analysis of the complex between citrate and the zinc peptidase carboxypeptidase A

Daniel Fernández, Ester Boix, Irantzu Pallarès, Francesc X. Avilés, Josep Vendrell

Producció científica: Contribució a una revistaArticleRecercaAvaluat per experts

12 Cites (Scopus)

Resum

A high-resolution carboxypeptidase-Zn2+-citrate complex was studied by X-ray diffraction and enzyme kinetics for the first time. The citrate molecule acts as a competitive inhibitor of this benchmark zinc-dependent peptidase, chelating the catalytic zinc ion in the active site of the enzyme and inducing a conformational change such that carboxypeptidase adopts the conformation expected to occur by substrate binding. Citrate adopts an extended conformation with half of the molecule facing the zinc ion, while the other half is docked in the S1′ hydrophobic specificity pocket of the enzyme, in contrast with the binding mode expected for a substrate like phenylalanine or a peptidomimetic inhibitor like benzylsuccinic acid. Combined structural and enzymatic analysis describes the characteristics of the binding of this ligand that, acting against physiologically relevant zinc-dependent proteases, may serve as a general model in the design of new drug-protecting molecules for the oral delivery of drugs of peptide origin. © 2011 Daniel Fernández et al.
Idioma originalEnglish
Número d’article128676
Pàgines (de-a)128-
RevistaEnzyme Research
Volum2011
DOIs
Estat de la publicacióPublicada - 1 de des. 2011

Fingerprint

Navegar pels temes de recerca de 'Structural and functional analysis of the complex between citrate and the zinc peptidase carboxypeptidase A'. Junts formen un fingerprint únic.

Com citar-ho