TY  - JOUR
PY  - 2009//
TI  - Structural insights into the alanine racemase from Enterococcus faecalis
JO  - Biochimica et biophysica acta
A1  - Priyadarshi, Amit
A1  - Lee, Eun Hye
A1  - Sung, Min Woo
A1  - Nam, Ki Hyun
A1  - Lee, Won Ho
A1  - Kim, Eunice Eunkyeong
A1  - Hwang, Kwang Yeon
SP  - 1030
EP  - 1040
VL  - 1794
IS  - 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 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.<p /> <p>Language: en</p>
LA  - en
SN  - 0006-3002
UR  - http://dx.doi.org/10.1016/j.bbapap.2009.03.006
ID  - ref1
ER  -