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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 A, 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.

Original publication

DOI

10.1107/s1744309108007252

Type

Journal article

Journal

Acta crystallographica. Section F, Structural biology and crystallization communications

Publication Date

05/2008

Volume

64

Pages

327 - 333

Addresses

Oxford Protein Production Facility, The Henry Wellcome Building for Genomic Medicine, Oxford University, Roosevelt Drive, Oxford OX3 7BN, England.

Keywords

Bacillus anthracis, Aminoethylphosphonic Acid, Alanine Racemase, Crystallography, X-Ray, Binding Sites, Molecular Structure, Amino Acid Sequence, Protein Conformation, Sequence Homology, Amino Acid, Methylation, Stereoisomerism, Molecular Sequence Data