Computer Modelling Reveals New Conformers of the ATP Binding Loop of Na+/K+-ATPase Involved in the Transphosphorylation Process of the Sodium Pump

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68407700%3A21720%2F17%3A00327507" target="_blank" >RIV/68407700:21720/17:00327507 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/68378041:_____/17:00477214 RIV/00216208:11130/17:10373843 RIV/62157124:16170/17:43875785

Výsledek na webu

<a href="http://dx.doi.org/10.7717/peerj.3087" target="_blank" >http://dx.doi.org/10.7717/peerj.3087</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.7717/peerj.3087" target="_blank" >10.7717/peerj.3087</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Computer Modelling Reveals New Conformers of the ATP Binding Loop of Na+/K+-ATPase Involved in the Transphosphorylation Process of the Sodium Pump

Popis výsledku v původním jazyce

Hydrolysis of ATP by Na+/K+-ATPase, a P-Type ATPase, catalyzing active Na+ and K+ transport through cellular membranes leads transiently to a phosphorylation of its catalytical alpha-subunit. Surprisingly, three-dimensional molecular structure analysis of P-type ATPases reveals that binding of ATP to the N-domain connected by a hinge to the P-domain is much too far away from the Asp(369) to allow the transfer of ATP's terminal phosphate to its aspartyl-phosphorylation site. In order to get information for how the transfer of the gamma-phosphate group of ATP to the Asp(369) is achieved, analogous molecular modeling of the M-4 M-5 loop of ATPase was performed using the crystal data of Na+/K+-ATPase of different species. Analogous molecular modeling of the cytoplasmic loop between Thr(338) and Ile(760) of the a alpha-subunit of Na+/K+-ATPase and the analysis of distances between the ATP binding site and phosphorylation site revealed the existence of two ATP binding sites in the open conformation; the first one close to Phe(475) in the N-domain, the other one close to Asp(369) in the 13-domain. However, binding of Mg2+circle ATP to any of these sites in the "open conformation" may not lead to phosphorylation of Asp(369). Additional conformations of the cytoplasmic loop were found wobbling between "open conformation" <==> "semi-open conformation <==> "closed conformation" in the absence of 2Mg(2+)circle ATP. The cytoplasmic loop's conformational change to the "semi-open conformation" characterized by a hydrogen bond between Arg(543) and Asp(611) triggers by binding of 2Mg(2+)circle ATP Ito a single ATP l site and conversion to the "closed l conformation" the phosphorylation of Asp(369) in the P-domain, and hence the start of Na+/K+-activated ATP hydrolysis.

Název v anglickém jazyce

Computer Modelling Reveals New Conformers of the ATP Binding Loop of Na+/K+-ATPase Involved in the Transphosphorylation Process of the Sodium Pump

Popis výsledku anglicky

Hydrolysis of ATP by Na+/K+-ATPase, a P-Type ATPase, catalyzing active Na+ and K+ transport through cellular membranes leads transiently to a phosphorylation of its catalytical alpha-subunit. Surprisingly, three-dimensional molecular structure analysis of P-type ATPases reveals that binding of ATP to the N-domain connected by a hinge to the P-domain is much too far away from the Asp(369) to allow the transfer of ATP's terminal phosphate to its aspartyl-phosphorylation site. In order to get information for how the transfer of the gamma-phosphate group of ATP to the Asp(369) is achieved, analogous molecular modeling of the M-4 M-5 loop of ATPase was performed using the crystal data of Na+/K+-ATPase of different species. Analogous molecular modeling of the cytoplasmic loop between Thr(338) and Ile(760) of the a alpha-subunit of Na+/K+-ATPase and the analysis of distances between the ATP binding site and phosphorylation site revealed the existence of two ATP binding sites in the open conformation; the first one close to Phe(475) in the N-domain, the other one close to Asp(369) in the 13-domain. However, binding of Mg2+circle ATP to any of these sites in the "open conformation" may not lead to phosphorylation of Asp(369). Additional conformations of the cytoplasmic loop were found wobbling between "open conformation" <==> "semi-open conformation <==> "closed conformation" in the absence of 2Mg(2+)circle ATP. The cytoplasmic loop's conformational change to the "semi-open conformation" characterized by a hydrogen bond between Arg(543) and Asp(611) triggers by binding of 2Mg(2+)circle ATP Ito a single ATP l site and conversion to the "closed l conformation" the phosphorylation of Asp(369) in the P-domain, and hence the start of Na+/K+-activated ATP hydrolysis.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30500 - Other medical sciences

Projekt

<a href="/cs/project/VI20152018010" target="_blank" >VI20152018010: Funkcionalizovaná nanovlákna pro sběr, identifikaci a dlouhodobé skladování pachových stop</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2017

Kód důvěrnosti údajů

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

Název periodika

PeerJ

ISSN

2167-8359

e-ISSN

2167-8359

Svazek periodika

5

Číslo periodika v rámci svazku

March

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

22

Strana od-do

—

Kód UT WoS článku

000396906100007

EID výsledku v databázi Scopus

2-s2.0-85015203992