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Structure and mechanism of glutamate racemase from Aquifex pyrophilus

Nature Structural Biology volume 6, pages 422–426 (1999)Cite this article

Abstract

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 Å resolution, reveals that the enzyme forms a dimer and each monomer consists of two α/β 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.

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Figure 1: a, A schematic ribbon diagram of the overall structure of a MurI monomer.
Figure 2: a, A stereo diagram showing the MurI dimer.
Figure 3: a, A 2Fo - Fc map showing the active-site region calculated at 2.3 Å resolution.

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Acknowledgements

We thank S.-H. Kim, T. Earnest and L.-W. Huang for help during data collection on the ALS (LBNL; Berkeley), and M. Tanner (UBC, Vancouver, BC) and J.-H. Yu (KIST) for helpful comments and critical reading of the manuscript. The Macromolecular Crystallography facility at beamline 5.0.2 in the ALS is principally funded by the Office of Biological and Environmental Research (US Department of Energy), with contributions from LBNL, Amgen, Roche Biosciences, the University of California (Berkeley), and Lawrence Livermore National Laboratory. This work was supported by the KIST (KIST 2000 program), MOST (Biotech 2000 program) and KAST (young scientist award to Y.C.).

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  1. Kwang Yeon Hwang, Chun-Seok Cho and Ha-Chin Sung: Both authors contributed equally to the work

Authors and Affiliations

  1. Structural Biology Center, Korea Institute of Science and Technology (KIST), P.O. Box 131, Cheongryang, Seoul, 130-650, Seoul, South Korea

    Kwang Yeon Hwang, Chun-Seok Cho, Sang Suk Kim, Yeon Gyu Yu & Yunje Cho

  2. Department of Biotechnology, Korea University, Seoul, South Korea

    Chun-Seok Cho & Ha-Chin Sung

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  1. Kwang Yeon Hwang
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Correspondence to Yunje Cho.

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Hwang, K., Cho, CS., Kim, S. et al. Structure and mechanism of glutamate racemase from Aquifex pyrophilus . Nat Struct Mol Biol 6, 422–426 (1999). https://doi.org/10.1038/8223

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