Importance of Val567 on heme environment and substrate recognition of neuronal nitric oxide synthase

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15310%2F18%3A73588047" target="_blank" >RIV/61989592:15310/18:73588047 - isvavai.cz</a>

Výsledek na webu

<a href="https://febs.onlinelibrary.wiley.com/doi/full/10.1002/2211-5463.12503" target="_blank" >https://febs.onlinelibrary.wiley.com/doi/full/10.1002/2211-5463.12503</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1002/2211-5463.12503" target="_blank" >10.1002/2211-5463.12503</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Importance of Val567 on heme environment and substrate recognition of neuronal nitric oxide synthase

Popis výsledku v původním jazyce

Nitric oxide (NO) produced by mammalian nitric oxide synthases (mNOSs) is an important mediator in a variety of physiological functions. Crystal structures of mNOSs have shown strong conservation of the active-site residue Val567 (numbering for rat neuronal NOS, nNOS). NOS-like proteins have been identified in several bacterial pathogens, and these display striking sequence identity to the oxygenase domain of mNOS (NOSoxy), with the exception of a Val to Ile mutation at the active site. Preliminary studies have highlighted the importance of this Val residue in NO-binding, substrate recognition, and oxidation in mNOSs. To further elucidate the role of this valine in substrate and substrate analogue recognition, we generated five Val567 mutants of the oxygenase domain of the neuronal NOS (nNOSoxy) and used UV-visible and EPR spectroscopy to investigate the effects of these mutations on the heme distal environment, the stability of the heme-Fe-II-CO complexes, and the binding of a series of substrate analogues. Our results are consistent with Val567 playing an important role in preserving the integrity of the active site for substrate binding, stability of heme-bound gaseous ligands, and potential NO production.

Název v anglickém jazyce

Importance of Val567 on heme environment and substrate recognition of neuronal nitric oxide synthase

Popis výsledku anglicky

Nitric oxide (NO) produced by mammalian nitric oxide synthases (mNOSs) is an important mediator in a variety of physiological functions. Crystal structures of mNOSs have shown strong conservation of the active-site residue Val567 (numbering for rat neuronal NOS, nNOS). NOS-like proteins have been identified in several bacterial pathogens, and these display striking sequence identity to the oxygenase domain of mNOS (NOSoxy), with the exception of a Val to Ile mutation at the active site. Preliminary studies have highlighted the importance of this Val residue in NO-binding, substrate recognition, and oxidation in mNOSs. To further elucidate the role of this valine in substrate and substrate analogue recognition, we generated five Val567 mutants of the oxygenase domain of the neuronal NOS (nNOSoxy) and used UV-visible and EPR spectroscopy to investigate the effects of these mutations on the heme distal environment, the stability of the heme-Fe-II-CO complexes, and the binding of a series of substrate analogues. Our results are consistent with Val567 playing an important role in preserving the integrity of the active site for substrate binding, stability of heme-bound gaseous ligands, and potential NO production.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

—

Návaznosti

N - Vyzkumna aktivita podporovana z neverejnych zdroju

Rok uplatnění

2018

Kód důvěrnosti údajů

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

Název periodika

FEBS Open Bio

ISSN

2211-5463

e-ISSN

—

Svazek periodika

8

Číslo periodika v rámci svazku

9

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

14

Strana od-do

1553-1566

Kód UT WoS článku

000443387400016

EID výsledku v databázi Scopus

2-s2.0-85052457250