Structures of an alanine racemase from Bacillus anthracis (BA0252) in the presence and absence of (R)-1-aminoethylphosphonic acid (L-Ala-P).

Journal article

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.

Authors: Au, K; Ren, J; Walter, T; Harlos, K; Nettleship, J

• Publication status: Published
• Journal: Acta crystallographica. Section F, Structural biology and crystallization communications
• Volume: 64
• Issue: Pt 5
• Pages: 327-333
• Publication date: 2008-05-01
• DOI: 10.1107/s1744309108007252
• EISSN: 1744-3091
• ISSN: 1744-3091
• Language: English
• Keywords: Aminoethylphosphonic Acid; Alanine Racemase; Methylation; Crystallography, X-Ray; Stereoisomerism; Molecular Structure; Sequence Homology, Amino Acid; Binding Sites; Molecular Sequence Data; Protein Conformation; Amino Acid Sequence; Bacillus anthracis