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

Acta Crystallogr Sect F Struct Biol Cryst Commun. 2008 May 1;64(Pt 5):327-33. doi: 10.1107/S1744309108007252. Epub 2008 Apr 5.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alanine Racemase / chemistry*
  • Alanine Racemase / genetics
  • Alanine Racemase / metabolism
  • Amino Acid Sequence
  • Aminoethylphosphonic Acid / pharmacology*
  • Bacillus anthracis / drug effects
  • Bacillus anthracis / enzymology*
  • Binding Sites
  • Crystallography, X-Ray
  • Methylation
  • Molecular Sequence Data
  • Molecular Structure
  • Protein Conformation
  • Sequence Homology, Amino Acid
  • Stereoisomerism

Substances

  • Aminoethylphosphonic Acid
  • Alanine Racemase