Structure of Nitric Oxide Synthase Oxygenase Dimer with Pterin and Substrate

• DOI: 10.1126/science.279.5359.2121
• Publication Date: 2002-07-27T09:49:42Z
• Authors: Brian R. Crane; Andrew S. Arvai; Dipak K. Ghosh; Chaoqun Wu; Elizabeth D. Getzoff; Dennis J. Stuehr; John A. Tainer
• Keywords: Pterin

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