Structural insights into the alanine racemase from Enterococcus faecalis.
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 A. 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.
Priyadarshi
Amit
A
Biomedical Research Center, Life Science Division, Korea Institute of Science and Technology, Seongbuk-gu, Seoul 136-791, South Korea.
Lee
Eun Hye
EH
Sung
Min Woo
MW
Nam
Ki Hyun
KH
Lee
Won Ho
WH
Kim
Eunice Eunkyeong
EE
Hwang
Kwang Yeon
KY