The Structure of the Aeromonas proteolytica Aminopeptidase Complexed with a Hydroxamate Inhibitor
Open Access
- 1 April 1996
- journal article
- Published by Wiley in European Journal of Biochemistry
- Vol. 237 (2), 393-398
- https://doi.org/10.1111/j.1432-1033.1996.0393k.x
Abstract
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.Keywords
This publication has 30 references indexed in Scilit:
- The CCP4 suite: programs for protein crystallographyActa Crystallographica Section D-Biological Crystallography, 1994
- MINIMAGE: a program for plotting electron-density mapsJournal of Applied Crystallography, 1994
- Site of Ionization of Hydroxamic Acids Probed by Heteronuclear NMR Relaxation Rate and NOE Measurements. An Experimental and Theoretical StudyJournal of the American Chemical Society, 1994
- Structure and Mechanism of Bovine Lens Leucine AminopeptidasePublished by Wiley ,1994
- Re-refinement of the X-ray Crystal Structure of Bovine Lens Leucine Aminopeptidase Complexed with BestatinJournal of Molecular Biology, 1993
- Structure determination and refinement of bovine lens leucine aminopeptidase and its complex with bestatinJournal of Molecular Biology, 1992
- Carboxypeptidase AAccounts of Chemical Research, 1989
- The thermodynamic metal–ligand stability constants of hydroxamic acids with some divalent metal ionsJournal of the Chemical Society, Perkin Transactions 2, 1989
- Structural basis of the action of thermolysin and related zinc peptidasesAccounts of Chemical Research, 1988
- Modified activity of Aeromonas aminopeptidase: metal ion substitutions and role of substratesBiochemistry, 1986