Linked Life Data

11473123

Source:http://linkedlifedata.com/resource/pubmed/id/11473123

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
40
pubmed:dateCreated
2001-10-1
pubmed:databankReference
pubmed:abstractText
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.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
5
pubmed:volume
276
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
37506-13
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:11473123-Amino Acid Sequence, pubmed-meshheading:11473123-Animals, pubmed-meshheading:11473123-Binding Sites, pubmed-meshheading:11473123-Crystallization, pubmed-meshheading:11473123-Crystallography, X-Ray, pubmed-meshheading:11473123-Flavin Mononucleotide, pubmed-meshheading:11473123-Flavin-Adenine Dinucleotide, pubmed-meshheading:11473123-Flavoproteins, pubmed-meshheading:11473123-Molecular Sequence Data, pubmed-meshheading:11473123-NADP, pubmed-meshheading:11473123-Nitric Oxide Synthase, pubmed-meshheading:11473123-Nitric Oxide Synthase Type I, pubmed-meshheading:11473123-Oxidoreductases, pubmed-meshheading:11473123-Protein Conformation, pubmed-meshheading:11473123-Protein Structure, Tertiary, pubmed-meshheading:11473123-Rats, pubmed-meshheading:11473123-Sequence Homology, Amino Acid
pubmed:year
2001
pubmed:articleTitle
Crystal structure of the FAD/NADPH-binding domain of rat neuronal nitric-oxide synthase. Comparisons with NADPH-cytochrome P450 oxidoreductase.
pubmed:affiliation
Department of Biochemistry, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't