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Structure of nitric oxide synthase oxygenase dimer with pterin and substrate

Academic Article
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Overview

authors

  • Crane, Brian R
  • Arvai, A. S.
  • Ghosh, D. K.
  • Wu, Chunlei
  • Getzoff, Elizabeth
  • Stuehr, D. J.
  • Tainer, John

publication date

  • March 1998

journal

  • Science  Journal

abstract

  • Crystal structures of the murine cytokine-inducible nitric oxide synthase oxygenase dimer with active-center water molecules, the substrate L-arginine (L-Arg), or product analog thiocitrulline reveal how dimerization, cofactor tetrahydrobiopterin, and L-Arg binding complete the catalytic center for synthesis of the essential biological signal and cytotoxin nitric oxide. Pterin binding refolds the central interface region, recruits new structural elements, creates a 30 angstrom deep active-center channel, and causes a 35 degrees helical tilt to expose a heme edge and the adjacent residue tryptophan-366 for likely reductase domain interactions and caveolin inhibition. Heme propionate interactions with pterin and L-Arg suggest that pterin has electronic influences on heme-bound oxygen. L-Arginine binds to glutamic acid-371 and stacks with heme in an otherwise hydrophobic pocket to aid activation of heme-bound oxygen by direct proton donation and thereby differentiate the two chemical steps of nitric oxide synthesis.

subject areas

  • Animals
  • Arginine
  • Binding Sites
  • Biopterin
  • Citrulline
  • Crystallography, X-Ray
  • Dimerization
  • Hydrogen Bonding
  • Isoenzymes
  • Ligands
  • Macrophages
  • Mice
  • Models, Molecular
  • Nitric Oxide
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type II
  • Protein Conformation
  • Protein Folding
  • Protein Structure, Secondary
  • Thiourea
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Identity

International Standard Serial Number (ISSN)

  • 0036-8075

Digital Object Identifier (DOI)

  • 10.1126/science.279.5359.2121

PubMed ID

  • 9516116
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Additional Document Info

start page

  • 2121

end page

  • 2126

volume

  • 279

issue

  • 5359

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