DOI: 10.1101/502799Dec 20, 2018Paper

Dynamics-function relationship of N-terminal acetyltransferases: the β6β7 loop modulates substrate accessibility to the catalytic site

BioRxiv : the Preprint Server for Biology
Angèle AbboudNathalie Reuter

Abstract

N-terminal acetyltransferases (NATs) are enzymes catalysing the transfer of the acetyl from Ac-CoA to the N-terminus of proteins, one of the most common protein modifications. Unlike NATs, lysine acetyltransferases (KATs) transfer an acetyl onto the amine group of internal lysines. To date, not much is known on the exclusive substrate specificity of NATs towards protein N-termini. All the NATs and some KATs share a common fold called GNAT. The main difference between NATs and KATs is an extra hairpin loop found only in NATs called β6β7 loop. It covers the active site as a lid. The hypothesized role of the loop is that of a barrier restricting the access to the catalytic site and preventing acetylation of internal lysines. We investigated the dynamics-function relationships of all available structures of NATs covering the three domains of life. Using elastic network models and normal mode analysis, we found a common dynamics pattern conserved through the GNAT fold; a rigid V-shaped groove, formed by the β4 and β5 strands and three relatively more dynamic loops α1α2, β3β4 and β6β7. We identified two independent dynamical domains in the GNAT fold, which is split at the β5 strand. We characterized the β6β7 hairpin loop slow dynamic...Continue Reading

Related Concepts

Acetylation
Ligands
Lysine
acetyldithio-coenzyme A
Protein N-terminal acetyltransferase
Site
Binding Protein
Lysine acetyltransferase
Shapes
Loop Diuretics

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