Comparative Modelling of Organic Anion Transporting Polypeptides: Structural Insights and Comparison of Binding Modes

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F22%3A00565955" target="_blank" >RIV/61388963:_____/22:00565955 - isvavai.cz</a>

Výsledek na webu

<a href="https://doi.org/10.3390/molecules27238531" target="_blank" >https://doi.org/10.3390/molecules27238531</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3390/molecules27238531" target="_blank" >10.3390/molecules27238531</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Comparative Modelling of Organic Anion Transporting Polypeptides: Structural Insights and Comparison of Binding Modes

Popis výsledku v původním jazyce

To better understand the functionality of organic anion transporting polypeptides (OATPs) and to design new ligands, reliable structural data of each OATP is needed. In this work, we used a combination of homology model with molecular dynamics simulations to generate a comprehensive structural dataset, that encompasses a diverse set of OATPs but also their relevant conformations. Our OATP models share a conserved transmembrane helix folding harbouring a druggable binding pocket in the shape of an inner pore. Our simulations suggest that the conserved salt bridges at the extracellular region between residues on TM1 and TM7 might influence the entrance of substrates. Interactions between residues on TM1 and TM4 within OATP1 family shown their importance in transport of substrates. Additionally, in transmembrane (TM) 1/2, a known conserved element, interact with two identified motifs in the TM7 and TM11. Our simulations suggest that TM1/2-TM7 interaction influence the inner pocket accessibility, while TM1/2-TM11 salt bridges control the substrate binding stability.

Název v anglickém jazyce

Comparative Modelling of Organic Anion Transporting Polypeptides: Structural Insights and Comparison of Binding Modes

Popis výsledku anglicky

To better understand the functionality of organic anion transporting polypeptides (OATPs) and to design new ligands, reliable structural data of each OATP is needed. In this work, we used a combination of homology model with molecular dynamics simulations to generate a comprehensive structural dataset, that encompasses a diverse set of OATPs but also their relevant conformations. Our OATP models share a conserved transmembrane helix folding harbouring a druggable binding pocket in the shape of an inner pore. Our simulations suggest that the conserved salt bridges at the extracellular region between residues on TM1 and TM7 might influence the entrance of substrates. Interactions between residues on TM1 and TM4 within OATP1 family shown their importance in transport of substrates. Additionally, in transmembrane (TM) 1/2, a known conserved element, interact with two identified motifs in the TM7 and TM11. Our simulations suggest that TM1/2-TM7 interaction influence the inner pocket accessibility, while TM1/2-TM11 salt bridges control the substrate binding stability.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10401 - Organic chemistry

Projekt

<a href="/cs/project/EF20_079%2F0017783" target="_blank" >EF20_079/0017783: UOCHB MSCA Mobility IV</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2022

Kód důvěrnosti údajů

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

Název periodika

Molecules

ISSN

1420-3049

e-ISSN

1420-3049

Svazek periodika

27

Číslo periodika v rámci svazku

23

Stát vydavatele periodika

CH - Švýcarská konfederace

Počet stran výsledku

18

Strana od-do

8531

Kód UT WoS článku

000896224500001

EID výsledku v databázi Scopus

2-s2.0-85143691748