Structural insights into the alanine racemase from Enterococcus faecalis

Amit Priyadarshi, Eun Hye Lee, Min Woo Sung, Ki Hyun Nam, Won Ho Lee, Eunice EunKyeong Kim, Kwang Yeon Hwang

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Alanine racemase (AlaR) is a bacterial enzyme that belongs to the fold-type III group of pyridoxal 5′-phosphate (PLP)-dependent enzymes. AlaR catalyzes the interconversion between l- and d-alanine, which is important for peptidoglycan biosynthesis. This enzyme is common in prokaryotes, but absent in eukaryotes, which makes it an attractive target for the design of new antibacterial drugs. Here, we report the crystal structures of both the apoenzyme and the d-cycloserine (DCS) complex of AlaR from the pathogenic bacterium Enterococcus faecalis v583, at a resolution of 2.5 Å. DCS is a suicide inhibitor of AlaR and, as such, serves as an antimicrobial agent and has been used to treat tuberculosis and urinary tract infection-related diseases, and makes several hydrogen bonds with the conserved active site residues, Tyr44 and Ser207, respectively. The apoenzyme crystal structure of AlaR consists of three monomers in the asymmetric unit, including a polyethylene glycol molecule in the dimer interface that surrounds one of the His 293 residues and also sits close to one side of the His 293 residue in the opposite monomer. Our results provide structural insights into AlaR that may be used for the development of new antibiotics targeting the alanine racemase in pathogenic bacteria.

Original languageEnglish
Pages (from-to)1030-1040
Number of pages11
JournalBiochimica et Biophysica Acta - Proteins and Proteomics
Volume1794
Issue number7
DOIs
Publication statusPublished - 2009 Jul 1

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Keywords

  • Alanine racemase
  • d-cycloserine
  • Enterococcus faecalis
  • PEG
  • PLP

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Analytical Chemistry
  • Molecular Biology

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