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

Kód výsledku v 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>

Výsledek na webu

<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>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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

Název v anglickém jazyce

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

Popis výsledku anglicky

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

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

CE - Biochemie

OECD FORD obor

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Projekt

—

Návaznosti

Z - Vyzkumny zamer (s odkazem do CEZ)

Rok uplatnění

2013

Kód důvěrnosti údajů

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

Název periodika

Biochemistry

ISSN

0006-2960

e-ISSN

—

Svazek periodika

52

Číslo periodika v rámci svazku

18

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

12

Strana od-do

3062-3073

Kód UT WoS článku

000318756300008

EID výsledku v databázi Scopus

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