A connecting hinge represses the activity of endothelial nitric oxide synthase.

A connecting hinge represses the activity of endothelial nitric oxide synthase. Research Abstract Details 

Research Abstract Table of Contents

Jump to the:

A connecting hinge represses the activity of endothelial nitric oxide synthase. Abstract Text:

Mohammad Mahfuzul Haque,Koustubh Panda, Tejero,Kulwant S Aulak,Mohammed Adam Fadlalla,Anthony T Mustovich,Dennis J Stuehr,

In mammals, endothelial nitric oxide synthase (eNOS) has the weakest activity, being one-tenth and one-sixth as active as the inducible NOS (iNOS) and the neuronal NOS (nNOS), respectively. The basis for this weak activity is unclear. We hypothesized that a hinge element that connects the FMN module in the reductase domain but is shorter and of unique composition in eNOS may be involved. To test this hypothesis, we generated an eNOS chimera that contained the nNOS hinge and two mutants that either eliminated (P728IeNOS) or incorporated (I958PnNOS) a proline residue unique to the eNOS hinge. Incorporating the nNOS hinge into eNOS increased NO synthesis activity 4-fold, to an activity two-thirds that of nNOS. It also decreased uncoupled NADPH oxidation, increased the apparent K(m)O(2) for NO synthesis, and caused a faster heme reduction. Eliminating the hinge proline had similar, but lesser, effects. Our findings reveal that the hinge is an important regulator and show that differences in its composition restrict the activity of eNOS relative to other NOS enzymes.

A connecting hinge represses the activity of endothelial nitric oxide synthase. Publishing Authors By Initials

MM Haque,K Panda,J Tejero,KS Aulak,MA Fadlalla,AT Mustovich,DJ Stuehr,

For similar investigative techniques: genetic techniques: sequence alignment research abstracts see: investigative techniques: genetic techniques: sequence alignment research

PUBMED ID PMID:

MEDLINE DATE:

A connecting hinge represses the activity of endothelial nitric oxide synthase. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Proceedings of the National Academy of Sciences of

VOLUME: 104

Page Numbers: 9254-9

Journal Abbreviation: Proc. Natl. Acad. Sci. U.S.A.

ISSN: 0027-8424

DAY: 21

MONTH: 05

YEAR: 2007

A connecting hinge represses the activity of endothelial nitric oxide synthase. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 7505876

A connecting hinge represses the activity of endothelial nitric oxide synthase. Keywords Mesh Terms:

KEYWORDS: Sequence Alignment

MESH TERMS: metabolism

Chemical & Substance for Abstract: A connecting hinge represses the activity of endothelial nitric oxide synthase. Information

Substance Name: Cytochrome Reductases

Registry Number: EC 1.6.2.-

Grant and Affiliation Information for A connecting hinge represses the activity of endothelial nitric oxide synthase.

AFFILIATION: Department of Pathobiology, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA.

Country: United States

AGENCY: United States NHLBI

GRANT: HL 076491

ACRONYM: HL

MEDLINETA: Proc Natl Acad Sci U S A

REFSOURCE:

DATABASENAME:

ACCESSION NUMBER:

Number Hits: 0

A connecting hinge represses the activity of endothelial nitric oxide synthase Related Publications

• A connecting hinge represses the activity of endothelial nitric oxide synthase.
• BYK191023 (2-[2-(4-methoxy-pyridin-2-yl)-ethyl]-3h-imidazo[4,5-b]pyridine) is an NADPH- and time-dependent irreversible inhibitor of inducible nitric-oxide synthase.
• Bacterial flavodoxins support nitric oxide production by Bacillus subtilis nitric-oxide synthase.
• Catalytic Reduction of a Tetrahydrobiopterin Radical within Nitric-oxide Synthase.
• Differences in a Conformational Equilibrium Distinguish Catalysis by the Endothelial and Neuronal Nitric-oxide Synthase Flavoproteins.
• Oxygenase domain of Drosophila melanogaster nitric oxide synthase: unique kinetic parameters enable a more efficient NO release.
• Surface charge interactions of the FMN module govern catalysis by nitric-oxide synthase.
• Versatile regulation of neuronal nitric oxide synthase by specific regions of its C-terminal tail.