Nitric oxide synthase dimeric structure

Li, H., Raman, C. S., Glaser, C. B., Blasko, E., Young,T. A., Parkinson, J. F., Whitlow, M., Poulos. T. L., Crystal structures of zinc-free and -bound heme domain of human inducible nitric-oxide synthase. Implications for dimer stability and comparison with endothelial nitric-oxide synthase, ]. Biol.Chem. 

Nitric oxide is synthesized from arginine in an NADPH-dependent reaction catalyzed by nitric oxide synthase (Fig. 22-31), a dimeric enzyme structurally related to NADPH cytochrome P-450 reductase (see Box 21-1). The reaction is a five-electron oxidation. Each subunit of the enzyme contains one bound molecule of each of four different cofactors FMN, FAD, tetrahydro-... 

In 1989, BH4 was found to be a cofactor for nitric oxide synthase (NOS) [ 126, 127]. BH4 is also involved in dimerization of NOS, as NOS is catalytically active in a homodimer structure. Three isoforms of NOS exist neuronal NOS (NOS 1), inducible NOS (NOS 2) and endothelial NOS (NOS 3). BH4 is essential for all NOS isoforms. The NOS isoforms share approximately 50-60% sequence homology. Each NOS polypeptide is comprised of oxygenase and reductase domains. An N-terminal oxygenase domain contains iron protoporphyrin IX (heme), BH4 and an arginine binding site, and a C-terminal reductase domain contains flavin mononucleotide (FMN), and a reduced nicotin-amide adenine dinucleotide phosphate (NADPH) binding site. 

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

Crane, B.R., A.S. Arvai, S. Ghosh, E.D. Getzoff, D.J. Stuehr, and J.A. Tainer (2000). Structures of the N-omega-hydroxy-L-arginine complex of inducible nitric oxide synthase oxygenase dimer with active and inactive pterins. Biochem. 39, 4608-4621. 

Klatt, P., Schmidt, K., Lehner, D., Clatter, O., Bachinger, H. P., and Mayer, B. (1995). Structural analysis of porcine brain nitric oxide synthase reveals a novel role of tetrahydrobiopterin and L-arginine in the formation of an SDS-resistant dimer. EMBO 7. (in press). 

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