Dynamics-function relationship in the catalytic domains of N-terminal acetyltransferases

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14330%2F20%3A00116312" target="_blank" >RIV/00216224:14330/20:00116312 - isvavai.cz</a>

Výsledek na webu

<a href="http://dx.doi.org/10.1016/j.csbj.2020.02.017" target="_blank" >http://dx.doi.org/10.1016/j.csbj.2020.02.017</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.csbj.2020.02.017" target="_blank" >10.1016/j.csbj.2020.02.017</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Dynamics-function relationship in the catalytic domains of N-terminal acetyltransferases

Popis výsledku v původním jazyce

N-terminal acetyltransferases (NATs) belong to the superfamily of acetyltransferases. They are enzymes catalysing the transfer of an acetyl group from acetyl coenzyme A to the N-terminus of polypeptide chains. N-terminal acetylation is one of the most common protein modifications. To date, not much is known on the molecular basis for the exclusive substrate specificity of NATs. All NATs share a common fold called GNAT. A characteristic of NATs is the beta6beta7 hairpin loop covering the active site and forming with the alpha1alpha2 loop a narrow tunnel surrounding the catalytic site in which cofactor and polypeptide meet and exchange an acetyl group. We investigated the dynamics-function relationships of all available structures of NATs covering the three domains of Life. Using an elastic network model and normal mode analysis, we found a common dynamics pattern conserved through the GNAT fold; a rigid V-shaped groove formed by the beta4 and beta5 strands and splitting the fold in two dynamical subdomains. Loops alpha1alpha2, beta3beta4 and beta6beta7 all show clear displacements in the low frequency normal modes. We characterized the mobility of the loops and show that even limited conformational changes of the loops along the low-frequency modes are able to significantly change the size and shape of the ligand binding sites. Based on the fact that these movements are present in most low-frequency modes, and common to all NATs, we suggest that the alpha1alpha2 and beta6beta7 loops may regulate ligand uptake and the release of the acetylated polypeptide.

Název v anglickém jazyce

Dynamics-function relationship in the catalytic domains of N-terminal acetyltransferases

Popis výsledku anglicky

N-terminal acetyltransferases (NATs) belong to the superfamily of acetyltransferases. They are enzymes catalysing the transfer of an acetyl group from acetyl coenzyme A to the N-terminus of polypeptide chains. N-terminal acetylation is one of the most common protein modifications. To date, not much is known on the molecular basis for the exclusive substrate specificity of NATs. All NATs share a common fold called GNAT. A characteristic of NATs is the beta6beta7 hairpin loop covering the active site and forming with the alpha1alpha2 loop a narrow tunnel surrounding the catalytic site in which cofactor and polypeptide meet and exchange an acetyl group. We investigated the dynamics-function relationships of all available structures of NATs covering the three domains of Life. Using an elastic network model and normal mode analysis, we found a common dynamics pattern conserved through the GNAT fold; a rigid V-shaped groove formed by the beta4 and beta5 strands and splitting the fold in two dynamical subdomains. Loops alpha1alpha2, beta3beta4 and beta6beta7 all show clear displacements in the low frequency normal modes. We characterized the mobility of the loops and show that even limited conformational changes of the loops along the low-frequency modes are able to significantly change the size and shape of the ligand binding sites. Based on the fact that these movements are present in most low-frequency modes, and common to all NATs, we suggest that the alpha1alpha2 and beta6beta7 loops may regulate ligand uptake and the release of the acetylated polypeptide.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10200 - Computer and information sciences

Projekt

—

Návaznosti

S - Specificky vyzkum na vysokych skolach

Rok uplatnění

2020

Kód důvěrnosti údajů

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

Název periodika

Computational and Structural Biology Journal

ISSN

2001-0370

e-ISSN

—

Svazek periodika

18

Číslo periodika v rámci svazku

1

Stát vydavatele periodika

NL - Nizozemsko

Počet stran výsledku

16

Strana od-do

532-547

Kód UT WoS článku

000607298800001

EID výsledku v databázi Scopus

2-s2.0-85081645026