Open AccessThe Structure of the Aeromonas proteolytica Aminopeptidase Complexed with a Hydroxamate Inhibitor
Author(s) -
Chevrier Bernard,
D'orchymont Hugues,
Schalk Céline,
Tarnus Céline,
Moras Dino
Publication year - 1996
Publication title -
european journal of biochemistry
Language(s) - English
Resource type - Journals
eISSN - 1432-1033
pISSN - 0014-2956
DOI - 10.1111/j.1432-1033.1996.0393k.x
Subject(s) - carboxylate , zinc , chemistry , molecule , stereochemistry , aminopeptidase , crystallography , hydrolase , crystal structure , phenylalanine , enzyme , amino acid , biochemistry , leucine , organic chemistry
The structure of the complex of Aeromonas proteolytica aminopeptidase, a two‐zinc exopeptidase, with the inhibitor p ‐iodo‐ d ‐phenylalanine hydroxamate has been determined by X‐ray crystallography. Refinement of the structure, which includes 220 water molecules, using data at 0.80–0.23‐nm resolution resulted in a crystallographic residual R value of 16%. The hydroxamate group adopts a planar conformation whereby the two oxygen atoms interact with the zinc ions. The N ‐hydroxyl group of the inhibitor is located between the two zinc ions, a position which is close to that occupied by a water molecule in the native structure. The carbonyl oxygen of the inhibitor binds to Zn1, which becomes pentacoordinated while Zn2 remains tetracoordinated, in contrast to the native protein where both zinc ions were shown to be tetracoordinated and structurally equivalent. Interactions of the carboxylate oxygens of Glu151 with the hydroxamate group play an important role in the stabilization of the complex.