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 language | English |
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Pages (from-to) | 1030-1040 |
Number of pages | 11 |
Journal | Biochimica et Biophysica Acta - Proteins and Proteomics |
Volume | 1794 |
Issue number | 7 |
DOIs | |
Publication status | Published - 2009 Jul |
Bibliographical note
Funding Information:We thank Dr. H. S. Lee and his staff for assistance during data collection at beamline 4A of Pohang Light Source, Korea. A. Priyadarshi and E. E Kim were supported by KIST grants. This study was supported by the Functional Proteomics Center, 21C Frontier Program of the Korea Ministry of Science and Technology.
Keywords
- Alanine racemase
- Enterococcus faecalis
- PEG
- PLP
- d-cycloserine
ASJC Scopus subject areas
- Analytical Chemistry
- Biophysics
- Biochemistry
- Molecular Biology