Methylated N-omega-Hydroxy-L-arginine Analogues as Mechanistic Probes for the Second Step of the Nitric Oxide Synthase-Catalyzed Reaction

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11110%2F13%3A10190178" target="_blank" >RIV/00216208:11110/13:10190178 - isvavai.cz</a>

Result on the web

<a href="http://dx.doi.org/10.1021/bi301571v" target="_blank" >http://dx.doi.org/10.1021/bi301571v</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1021/bi301571v" target="_blank" >10.1021/bi301571v</a>

Result language

angličtina

Original language name

Methylated N-omega-Hydroxy-L-arginine Analogues as Mechanistic Probes for the Second Step of the Nitric Oxide Synthase-Catalyzed Reaction

Original language description

Nitric oxide synthase (NOS) catalyzes the conversion of L-arginine to L-citrulline through the intermediate N-omega-hydroxy-L-arginine (NHA), producing nitric oxide, an important mammalian signaling molecule. Several disease states are associated with improper regulation of nitric oxide production, making NOS a therapeutic target. The first step of the NOS reaction has been well-characterized and is presumed to proceed through a compound I heme species, analogous to the cytochrome P450 mechanism. The second step, however, is enzymatically unprecedented and is thought to occur via a ferric peroxo heme species. To gain insight into the details of this unique second step, we report here the synthesis of NHA analogues bearing guanidinium methyl or ethyl substitutions and their investigation as either inhibitors of or alternate substrates for NOS. Radiolabeling studies reveal that N-omega-methoxy-L-arginine, an alternative NOS substrate, produces citrulline, nitric oxide, and methanol. On t

Czech name

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Czech description

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Type

J_x - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)

CEP classification

CE - Biochemistry

OECD FORD branch

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Project

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Continuities

Z - Vyzkumny zamer (s odkazem do CEZ)

Publication year

2013

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Biochemistry

ISSN

0006-2960

e-ISSN

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Volume of the periodical

52

Issue of the periodical within the volume

18

Country of publishing house

US - UNITED STATES

Number of pages

12

Pages from-to

3062-3073

UT code for WoS article

000318756300008

EID of the result in the Scopus database

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