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N-terminal domain swapping and metal ion binding in nitric oxide synthase dimerization

Academic Article
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Overview

related to degree

  • Gunn, Robin Rosenfeld, Ph.D. in Biology, Scripps Research 1995 - 2002

authors

  • Crane, Brian R
  • Gunn, Robin Rosenfeld
  • Arvai, A. S.
  • Ghosh, D. K.
  • Ghosh, S.
  • Tainer, John
  • Stuehr, D. J.
  • Getzoff, Elizabeth

publication date

  • November 1999

journal

  • EMBO Journal  Journal

abstract

  • Nitric oxide synthase oxygenase domains (NOS(ox)) must bind tetrahydrobiopterin and dimerize to be active. New crystallographic structures of inducible NOS(ox) reveal that conformational changes in a switch region (residues 103-111) preceding a pterin-binding segment exchange N-terminal beta-hairpin hooks between subunits of the dimer. N-terminal hooks interact primarily with their own subunits in the 'unswapped' structure, and two switch region cysteines (104 and 109) from each subunit ligate a single zinc ion at the dimer interface. N-terminal hooks rearrange from intra- to intersubunit interactions in the 'swapped structure', and Cys109 forms a self-symmetric disulfide bond across the dimer interface. Subunit association and activity are adversely affected by mutations in the N-terminal hook that disrupt interactions across the dimer interface only in the swapped structure. Residue conservation and electrostatic potential at the NOS(ox) molecular surface suggest likely interfaces outside the switch region for electron transfer from the NOS reductase domain. The correlation between three-dimensional domain swapping of the N-terminal hook and metal ion release with disulfide formation may impact inducible nitric oxide synthase (i)NOS stability and regulation in vivo.

subject areas

  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Conserved Sequence
  • Crystallography, X-Ray
  • Cysteine
  • Dimerization
  • Hydrogen Bonding
  • Macromolecular Substances
  • Mice
  • Models, Molecular
  • Molecular Sequence Data
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type II
  • Protein Structure, Quaternary
  • Protein Structure, Secondary
  • Recombinant Proteins
  • Software
  • Static Electricity
  • Zinc
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Research

keywords

  • X-ray structure
  • beta-hairpin
  • disulfide
  • domain swapping
  • zinc
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Identity

PubMed Central ID

  • PMC1171690

International Standard Serial Number (ISSN)

  • 0261-4189

Digital Object Identifier (DOI)

  • 10.1093/emboj/18.22.6271

PubMed ID

  • 10562539
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Additional Document Info

start page

  • 6271

end page

  • 6281

volume

  • 18

issue

  • 22

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