Structure of nitric oxide synthase oxygenase dimer with pterin and substrate.
Science
; 279(5359): 2121-6, 1998 Mar 27.
Article
em En
| MEDLINE
| ID: mdl-9516116
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.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Arginina
/
Conformação Proteica
/
Biopterinas
/
Óxido Nítrico Sintase
Limite:
Animals
Idioma:
En
Revista:
Science
Ano de publicação:
1998
Tipo de documento:
Article
País de afiliação:
Estados Unidos