Structure and mechanism of glutamate racemase from Aquifex pyrophilus

• Published in: Nature structural biology Vol. 6; no. 5; pp. 422 - 426
• Main Authors: Cho, Yunje, Hwang, Kwang Yeon, Cho, Chun-Seok, Kim, Sang Suk, Sung, Ha-Chin, Yu, Yeon Gyu
• Format: Journal Article
• Language: English
• Published: United States 01-05-1999
• Subjects: Amino Acid Isomerases - chemistry; Amino Acid Isomerases - genetics; Amino Acid Isomerases - metabolism; Amino Acid Sequence; Amino Acid Substitution; Apoenzymes - chemistry; Apoenzymes - metabolism; Aquifex pyrophilus; Binding Sites; Catalysis; Crystallography, X-Ray; Cysteine - chemistry; Cysteine - metabolism; Dimerization; Glutamic acid; Glutamine - chemistry; Glutamine - metabolism; Gram-Negative Aerobic Rods and Cocci - enzymology; Gram-Negative Aerobic Rods and Cocci - genetics; Kinetics; Models, Chemical; Models, Molecular; Molecular Sequence Data; Phosphopyruvate Hydratase - chemistry; Protein Binding; Protein Conformation; Protein Structure, Secondary
• ISSN: 1072-8368; 2331-365X
• DOI: 10.1038/8223

Glutamate racemase (MurI) is responsible for the synthesis of D-glutamate, an essential building block of the peptidoglycan layer in bacterial cell walls. The crystal structure of glutamate racemase from Aquifex pyrophilus, determined at 2.3 A resolution, reveals that the enzyme forms a dimer and each monomer consists of two alpha/beta fold domains, a unique structure that has not been observed in other racemases or members of an enolase superfamily. A substrate analog, D-glutamine, binds to the deep pocket formed by conserved residues from two monomers. The structural and mutational analyses allow us to propose a mechanism of metal cofactor-independent glutamate racemase in which two cysteine residues are involved in catalysis.