Kim, Kook-Han Bong, Young-Jong Park, Joon Kyu Shin, Key-Jung Hwang, Kwang Yeon Kim, Eunice EunKyeong 2024-01-21T00:32:03Z 2024-01-21T00:32:03Z 2021-09-02 2007-09-14 0022-2836 https://pubs.kist.re.kr/handle/201004/134105 D-Glutamic acid is a required biosynthetic building block for peptidoglycan, and the enzyme glutamate racemase (GluR) catalyzes the inter-conversion of D and L-glutamate enantiomers. Therefore, GluR is considered as an attractive target for the design of new antibacterial drugs. Here, we report the crystal structures of GluR from Streptococcus pyogenes in both inhibitorfree and inhibitor-bound forms. The inhibitor free GluR crystallized in two different forms, which diffracted to 2.25 angstrom and 2.5 angstrom resolution, while the inhibitor-bound crystal diffracted to 2.5 A resolution. GluR is composed of two domains of alpha/beta protein that are related by pseudo-2-fold symmetry and the active site is located at the domain interface. The inhibitor, gamma-2-naphthylmethyl-D-glutamate, which was reported earlier as a novel potent competitive inhibitor, makes several hydrogen bonds with protein atoms, and the naphthyl moiety is located in the hydrophobic pocket. The inhibitor binding induces a disorder in one of the loops near the active site. In both crystal forms, GluR exists as a dimer and the interactions seen at the dimer interface are almost identical. This agrees well with the results from gel filtration and dynamic light-scattering studies. (C) 2007 Published by Elsevier Ltd. English ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD D-AMINO ACIDS LACTOBACILLUS-FERMENTI ASPARTATE RACEMASE CRYSTAL-STRUCTURE ESCHERICHIA-COLI MECHANISM PURIFICATION RESIDUES MURI IDENTIFICATION Structural basis for glutamate racemase inhibition Article 10.1016/j.jmb.2007.05.003 1 JOURNAL OF MOLECULAR BIOLOGY, v.372, no.2, pp.434 - 443 JOURNAL OF MOLECULAR BIOLOGY 372 2 434 443 scie scopus 000249372200013 2-s2.0-34547932250 Biochemistry & Molecular Biology Biochemistry & Molecular Biology Article D-AMINO ACIDS LACTOBACILLUS-FERMENTI ASPARTATE RACEMASE CRYSTAL-STRUCTURE ESCHERICHIA-COLI MECHANISM PURIFICATION RESIDUES MURI IDENTIFICATION D-glutamic acid glutamate racemase antibacterial crystal structure