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Nature Structural Biology  5, 369 - 376 (1998)
doi:10.1038/nsb0598-369

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

Mary A. Turner1, Chong-Sheng Yuan2, 3, Ronald T. Borchardt2, Michael S. Hershfield4, G. David Smith5, 6 & P. Lynne Howell1, 7, 8

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

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

  3Present address: Tanabe Research Laboratories USA Inc., 4540 Towne Center Court, San Diego, California 92121, USA.

  4Departments of Medicine and Biochemistry, Duke University Medical Center, Durham, North Carolina 77071, USA.

  5Hauptman-Woodward Medical Research Institute, 73 High Street, Buffalo, New York 14203, USA.

  6Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, New York 14263, USA.

  7Department of Biochemistry, Faculty of Medicine, University of Toronto, Medical Sciences Building, Toronto, M5S 1A8, Ontario, Canada.

  8email: howell@sickkids.on.ca

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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Nature Structural & Molecular Biology
ISSN: 1545-9993
EISSN: 1545-9985
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