1f20
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CRYSTAL STRUCTURE OF RAT NEURONAL NITRIC-OXIDE SYNTHASE FAD/NADP+ DOMAIN AT 1.9A RESOLUTION.
OverviewOverview
Nitric-oxide synthase (NOS) is composed of a C-terminal, flavin-containing, reductase domain and an N-terminal, heme-containing oxidase domain. The, reductase domain, similar to NADPH-cytochrome P450 reductase, can be, further divided into two different flavin-containing domains: (a) the N, terminus, FMN-containing portion, and (b) the C terminus FAD- and, NADPH-binding portion. The crystal structure of the FAD/NADPH-containing, domain of rat neuronal nitric-oxide synthase, complexed with NADP(+), has, been determined at 1.9 A resolution. The protein is fully capable of, reducing ferricyanide, using NADPH as the electron donor. The overall, polypeptide fold of the domain is very similar to that of the, corresponding module of NADPH-cytochrome P450 oxidoreductase (CYPOR) and, consists of three structural subdomains (from N to C termini): (a) the, connecting domain, (b) the FAD-binding domain, and (c) the NADPH-binding, domain. A comparison of the structure of the neuronal NOS FAD/NADPH domain, and CYPOR reveals the strict conservation of the flavin-binding site, including the tightly bound water molecules, the mode of NADP(+) binding, and the aromatic residue that lies at the re-face of the flavin ring, strongly suggesting that the hydride transfer mechanisms in the two, enzymes are very similar. In contrast, the putative FMN domain-binding, surface of the NOS protein is less positively charged than that of its, CYPOR counterpart, indicating a different nature of interactions between, the two flavin domains and a different mode of regulation in electron, transfer between the two flavins involving the autoinhibitory element and, the C-terminal 33 residues, both of which are absent in CYPOR.
About this StructureAbout this Structure
1F20 is a Single protein structure of sequence from Rattus norvegicus with FAD, NAP, GOL and FMT as ligands. Active as Nitric-oxide synthase, with EC number 1.14.13.39 Full crystallographic information is available from OCA.
ReferenceReference
Crystal structure of the FAD/NADPH-binding domain of rat neuronal nitric-oxide synthase. Comparisons with NADPH-cytochrome P450 oxidoreductase., Zhang J, Martasek P, Paschke R, Shea T, Siler Masters BS, Kim JJ, J Biol Chem. 2001 Oct 5;276(40):37506-13. Epub 2001 Jul 25. PMID:11473123
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