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

ABBOUD, Angèle, Pierre BÉDOUCHA, Jan BYŠKA, Thomas ARNESEN and Nathalie REUTER. Dynamics-function relationship in the catalytic domains of N-terminal acetyltransferases. Computational and Structural Biology Journal. Netherlands: Elsevier, 2020, vol. 18, No 1, p. 532-547. ISSN 2001-0370. Available from: https://dx.doi.org/10.1016/j.csbj.2020.02.017.

Basic information

Original name

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

Authors

ABBOUD, Angèle (578 Norway), Pierre BÉDOUCHA (578 Norway), Jan BYŠKA (203 Czech Republic, belonging to the institution), Thomas ARNESEN (578 Norway) and Nathalie REUTER (578 Norway)

Edition

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

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Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10200 1.2 Computer and information sciences

Country of publisher

Netherlands

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 7.271

RIV identification code

RIV/00216224:14330/20:00116312

Organization unit

Faculty of Informatics

DOI

http://dx.doi.org/10.1016/j.csbj.2020.02.017

UT WoS

000607298800001

Keywords in English

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

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Abstract

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.