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Structure determination of selenomethionyl S-adenosylhomocysteine hydrolase using data at a single wavelength

Nature Structural Biology volume 5, pages 369–376 (1998)Cite this article

Abstract

S-Adenosylhomocysteine (AdoHcy) hydrolase regulates all adenosylmethionine-(AdoMet) dependent transmethylations by hydrolyzing the potent feedback inhibitor AdoHcy to homocysteine and adenosine. The crystallographic structure determination of a selenomethionyl-incorporated AdoHcy hydrolase inhibitor complex was accomplished using single wavelength anomalous diffraction data and the direct methods program, Snb v2.0, which produced the positions of all 30 crystallographically distinct selenium atoms. The mode of enzyme–cofactor binding is unique, requiring interactions from two protein monomers. An unusual dual role for a catalytic water molecule in the active site is revealed in the complex with the adenosine analog 2′-hydroxy, 3′-ketocyclopent-4′-enyladenine.

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Author information

Author notes

  1. Chong-Sheng Yuan

    Present address: Tanabe Research Laboratories USA Inc., 4540 Towne Center Court, San Diego, California, 92121, USA

Authors and Affiliations

  1. Structural Biology and Biochemistry, Research Institute, Hospital for Sick Children, 555 University Avenue, Toronto, M5G 1X8, Ontario, Canada

    Mary A. Turner & P. Lynne Howell

  2. Departments of Biochemistry and Pharmaceutical Chemistry, University of Kansas, Lawrence, Kansas, 66045, USA

    Chong-Sheng Yuan & Ronald T. Borchardt

  3. Departments of Medicine and Biochemistry, Duke University Medical Center, Durham, North Carolina, 77071, USA

    Michael S. Hershfield

  4. Hauptman-Woodward Medical Research Institute, 73 High Street, Buffalo, New York, 14203, USA

    G. David Smith

  5. Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, New York, 14263, USA

    G. David Smith

  6. Department of Biochemistry, Faculty of Medicine, University of Toronto, Medical Sciences Building, Toronto, M5S 1A8, Ontario, Canada

    P. Lynne Howell

Authors
  1. Mary A. Turner
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Correspondence to P. Lynne Howell.

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Turner, M., Yuan, CS., Borchardt, R. et al. Structure determination of selenomethionyl S-adenosylhomocysteine hydrolase using data at a single wavelength. Nat Struct Mol Biol 5, 369–376 (1998). https://doi.org/10.1038/nsb0598-369

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