Holoenzyme structures of endothelial nitric oxide synthase - An allosteric role for calmodulin in pivoting the FMN domain for electron transfer

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11110%2F14%3A10283778" target="_blank" >RIV/00216208:11110/14:10283778 - isvavai.cz</a>

Výsledek na webu

<a href="http://dx.doi.org/10.1016/j.jsb.2014.08.006" target="_blank" >http://dx.doi.org/10.1016/j.jsb.2014.08.006</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.jsb.2014.08.006" target="_blank" >10.1016/j.jsb.2014.08.006</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Holoenzyme structures of endothelial nitric oxide synthase - An allosteric role for calmodulin in pivoting the FMN domain for electron transfer

Popis výsledku v původním jazyce

While the three-dimensional structures of heme- and flavin-binding domains of the NOS isoforms have been determined, the structures of the holoenzymes remained elusive. Application of electron cryo-microscopy and structural modeling of the bovine endothelial nitric oxide synthase (eNOS) holoenzyme produced detailed models of the intact holoenzyme in the presence and absence of Ca2+/calmodulin (CaM). These models accommodate the cross-electron transfer from the reductase in one monomer to the heme in theopposite monomer. The heme domain acts as the anchoring dimeric structure for the entire enzyme molecule, while the FMN domain is activated by CaM to move flexibly to bridge the distance between the reductase and oxygenase domains. Our results indicatethat the key regulatory role of CaM involves the stabilization of structural intermediates and precise positioning of the pivot for the FMN domain tethered shuttling motion to accommodate efficient and rapid electron transfer in the homod

Název v anglickém jazyce

Holoenzyme structures of endothelial nitric oxide synthase - An allosteric role for calmodulin in pivoting the FMN domain for electron transfer

Popis výsledku anglicky

While the three-dimensional structures of heme- and flavin-binding domains of the NOS isoforms have been determined, the structures of the holoenzymes remained elusive. Application of electron cryo-microscopy and structural modeling of the bovine endothelial nitric oxide synthase (eNOS) holoenzyme produced detailed models of the intact holoenzyme in the presence and absence of Ca2+/calmodulin (CaM). These models accommodate the cross-electron transfer from the reductase in one monomer to the heme in theopposite monomer. The heme domain acts as the anchoring dimeric structure for the entire enzyme molecule, while the FMN domain is activated by CaM to move flexibly to bridge the distance between the reductase and oxygenase domains. Our results indicatethat the key regulatory role of CaM involves the stabilization of structural intermediates and precise positioning of the pivot for the FMN domain tethered shuttling motion to accommodate efficient and rapid electron transfer in the homod

Druh

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

CEP obor

CE - Biochemie

OECD FORD obor

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Projekt

<a href="/cs/project/ED1.1.00%2F02.0109" target="_blank" >ED1.1.00/02.0109: Biotechnologické a biomedicínské centrum Akademie věd a Univerzity Karlovy</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2014

Kód důvěrnosti údajů

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

Název periodika

Journal of Structural Biology

ISSN

1047-8477

e-ISSN

—

Svazek periodika

188

Číslo periodika v rámci svazku

1

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

9

Strana od-do

46-54

Kód UT WoS článku

000343354300006

EID výsledku v databázi Scopus

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