2NOD

MURINE INDUCIBLE NITRIC OXIDE SYNTHASE OXYGENASE DIMER (DELTA 65) WITH TETRAHYDROBIOPTERIN AND WATER BOUND IN ACTIVE CENTER

Summary for 2NOD

• Entry DOI: 10.2210/pdb2nod/pdb
• Descriptor: NITRIC OXIDE SYNTHASE, SULFATE ION, PROTOPORPHYRIN IX CONTAINING FE, ... (5 entities in total)
• Functional Keywords: oxidoreductase, nitric oxide l-arginine monooxygenase, heme, dimer, nos
• Biological source: Mus musculus (house mouse)
• Total number of polymer chains: 2
• Total formula weight: 99808.91

Authors

Crane, B.R.,Arvai, A.S.,Getzoff, E.D.,Stuehr, D.J.,Tainer, J.A. (deposition date: 1998-03-05, release date: 1999-03-23, Last modification date: 2024-10-30)

Primary citation

Crane, B.R.,Arvai, A.S.,Ghosh, D.K.,Wu, C.,Getzoff, E.D.,Stuehr, D.J.,Tainer, J.A.
Structure of nitric oxide synthase oxygenase dimer with pterin and substrate.
Science, 279:2121-2126, 1998

PubMed 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.

PubMed: 9516116
DOI: 10.1126/science.279.5359.2121

Experimental method

X-RAY DIFFRACTION (2.6 Å)