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

J 2020

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

ABBOUD, Angèle; Pierre BÉDOUCHA; Jan BYŠKA; Thomas ARNESEN; Nathalie REUTER et al.

Základní údaje

Originální název

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

Autoři

ABBOUD, Angèle; Pierre BÉDOUCHA; Jan BYŠKA ; Thomas ARNESEN a Nathalie REUTER

Vydání

Computational and Structural Biology Journal, Netherlands, Elsevier, 2020, 2001-0370

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

10200 1.2 Computer and information sciences

Stát vydavatele

Nizozemské království

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 7.271

Označené pro přenos do RIV

Ano

Kód RIV

RIV/00216224:14330/20:00116312

Organizační jednotka

Fakulta informatiky

Klíčová slova anglicky

Acetylation; Ligand specificity; N-terminal acetyltransferases; Normal modes analysis; Protein dynamics

Změněno: 10. 5. 2021 05:52, RNDr. Pavel Šmerk, Ph.D.

Anotace

V originále

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.

Citovat

ABBOUD, Angèle; Pierre BÉDOUCHA; Jan BYŠKA; Thomas ARNESEN a Nathalie REUTER. Dynamics-function relationship in the catalytic domains of N-terminal acetyltransferases. Computational and Structural Biology Journal. Netherlands: Elsevier, 2020, roč. 18, č. 1, s. 532-547. ISSN 2001-0370. Dostupné z: https://doi.org/10.1016/j.csbj.2020.02.017.

@article{1676653,
   author = {Abboud, Angèle and Bédoucha, Pierre and Byška, Jan and Arnesen, Thomas and Reuter, Nathalie},
   article_location = {Netherlands},
   article_number = {1},
   doi = {https://doi.org/10.1016/j.csbj.2020.02.017},
   keywords = {Acetylation; Ligand specificity; N-terminal acetyltransferases; Normal modes analysis; Protein dynamics},
   language = {eng},
   issn = {2001-0370},
   journal = {Computational and Structural Biology Journal},
   title = {Dynamics-function relationship in the catalytic domains of N-terminal acetyltransferases},
   url = {http://dx.doi.org/10.1016/j.csbj.2020.02.017},
   volume = {18},
   year = {2020}
}

TY  - JOUR
ID  - 1676653
AU  - Abboud, Angèle - Bédoucha, Pierre - Byška, Jan - Arnesen, Thomas - Reuter, Nathalie
PY  - 2020
TI  - Dynamics-function relationship in the catalytic domains of N-terminal acetyltransferases
JF  - Computational and Structural Biology Journal
VL  - 18
IS  - 1
SP  - 532-547
EP  - 532-547
PB  - Elsevier
SN  - 20010370
KW  - Acetylation
KW  - Ligand specificity
KW  - N-terminal acetyltransferases
KW  - Normal modes analysis
KW  - Protein dynamics
UR  - http://dx.doi.org/10.1016/j.csbj.2020.02.017
L2  - http://dx.doi.org/10.1016/j.csbj.2020.02.017
N2  - 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.
ER  -

ABBOUD, Angèle; Pierre BÉDOUCHA; Jan BYŠKA; Thomas ARNESEN a Nathalie REUTER. Dynamics-function relationship in the catalytic domains of N-terminal acetyltransferases. \textit{Computational and Structural Biology Journal}. Netherlands: Elsevier, 2020, roč.~18, č.~1, s.~532-547. ISSN~2001-0370. Dostupné z: https://doi.org/10.1016/j.csbj.2020.02.017.

Přehled o publikaci