Open AccessStructures of an alanine racemase from Bacillus anthracis (BA0252) in the presence and absence of ( R )‐1‐aminoethylphosphonic acid ( l ‐Ala‐P)
Author(s) -
Au Kinfai,
Ren Jingshan,
Walter Thomas S.,
Harlos Karl,
Nettleship Joanne E.,
Owens Raymond J.,
Stuart David I.,
Esnouf Robert M.
Publication year - 2008
Publication title -
acta crystallographica section f
Language(s) - English
Resource type - Journals
ISSN - 1744-3091
DOI - 10.1107/s1744309108007252
Subject(s) - bacillus anthracis , alanine , stereochemistry , chemistry , biochemistry , biology , amino acid , genetics , bacteria
Bacillus anthracis , the causative agent of anthrax, has been targeted by the Oxford Protein Production Facility to validate high‐throughput protocols within the Structural Proteomics in Europe project. As part of this work, the structures of an alanine racemase (BA0252) in the presence and absence of the inhibitor ( R )‐1‐aminoethylphosphonic acid ( l ‐Ala‐P) have determined by X‐ray crystallography to resolutions of 2.1 and 1.47 Å, respectively. Difficulties in crystallizing this protein were overcome by the use of reductive methylation. Alanine racemase has attracted much interest as a possible target for anti‐anthrax drugs: not only is d ‐alanine a vital component of the bacterial cell wall, but recent studies also indicate that alanine racemase, which is accessible in the exosporium, plays a key role in inhibition of germination in B. anthracis . These structures confirm the binding mode of l ‐Ala‐P but suggest an unexpected mechanism of inhibition of alanine racemase by this compound and could provide a basis for the design of improved alanine racemase inhibitors with potential as anti‐anthrax therapies.