TY - JOUR
T1 - Structural insights into the alanine racemase from Enterococcus faecalis
AU - Priyadarshi, Amit
AU - Lee, Eun Hye
AU - Sung, Min Woo
AU - Nam, Ki Hyun
AU - Lee, Won Ho
AU - Kim, Eunice Eun Kyeong
AU - Hwang, Kwang Yeon
N1 - 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.
PY - 2009/7
Y1 - 2009/7
N2 - 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.
AB - 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.
KW - Alanine racemase
KW - Enterococcus faecalis
KW - PEG
KW - PLP
KW - d-cycloserine
UR - http://www.scopus.com/inward/record.url?scp=67349206089&partnerID=8YFLogxK
U2 - 10.1016/j.bbapap.2009.03.006
DO - 10.1016/j.bbapap.2009.03.006
M3 - Article
C2 - 19328247
AN - SCOPUS:67349206089
SN - 1570-9639
VL - 1794
SP - 1030
EP - 1040
JO - Biochimica et Biophysica Acta - Proteins and Proteomics
JF - Biochimica et Biophysica Acta - Proteins and Proteomics
IS - 7
ER -