Acetyl group coordinated progression through the catalytic cycle of an arylalkylamine N-acetyltransferase.

The transfer of an acetyl group from acetyl-CoA to an acceptor amine is a ubiquitous biochemical transformation catalyzed by Gcn5-related N-acetyltransferases (GNATs). Although it is established that the reaction proceeds through a sequential ordered mechanism, the role of the acetyl group in drivin...

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Main Authors: Adam A Aboalroub, Ashleigh B Bachman, Ziming Zhang, Dimitra Keramisanou, David J Merkler, Ioannis Gelis
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2017-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC5423648?pdf=render
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spelling doaj-ae15601347b4436b93c0145d219e22bc2020-11-25T02:47:26ZengPublic Library of Science (PLoS)PLoS ONE1932-62032017-01-01125e017727010.1371/journal.pone.0177270Acetyl group coordinated progression through the catalytic cycle of an arylalkylamine N-acetyltransferase.Adam A AboalroubAshleigh B BachmanZiming ZhangDimitra KeramisanouDavid J MerklerIoannis GelisThe transfer of an acetyl group from acetyl-CoA to an acceptor amine is a ubiquitous biochemical transformation catalyzed by Gcn5-related N-acetyltransferases (GNATs). Although it is established that the reaction proceeds through a sequential ordered mechanism, the role of the acetyl group in driving the ordered formation of binary and ternary complexes remains elusive. Herein, we show that CoA and acetyl-CoA alter the conformation of the substrate binding site of an arylalkylamine N-acetyltransferase (AANAT) to facilitate interaction with acceptor substrates. However, it is the presence of the acetyl group within the catalytic funnel that triggers high affinity binding. Acetyl group occupancy is relayed through a conserved salt bridge between the P-loop and the acceptor binding site, and is manifested as differential dynamics in the CoA and acetyl-CoA-bound states. The capacity of the acetyl group carried by an acceptor to promote its tight binding even in the absence of CoA, but also its mutually exclusive position to the acetyl group of acetyl-CoA underscore its importance in coordinating the progression of the catalytic cycle.http://europepmc.org/articles/PMC5423648?pdf=render
collection DOAJ
language English
format Article
sources DOAJ
author Adam A Aboalroub
Ashleigh B Bachman
Ziming Zhang
Dimitra Keramisanou
David J Merkler
Ioannis Gelis
spellingShingle Adam A Aboalroub
Ashleigh B Bachman
Ziming Zhang
Dimitra Keramisanou
David J Merkler
Ioannis Gelis
Acetyl group coordinated progression through the catalytic cycle of an arylalkylamine N-acetyltransferase.
PLoS ONE
author_facet Adam A Aboalroub
Ashleigh B Bachman
Ziming Zhang
Dimitra Keramisanou
David J Merkler
Ioannis Gelis
author_sort Adam A Aboalroub
title Acetyl group coordinated progression through the catalytic cycle of an arylalkylamine N-acetyltransferase.
title_short Acetyl group coordinated progression through the catalytic cycle of an arylalkylamine N-acetyltransferase.
title_full Acetyl group coordinated progression through the catalytic cycle of an arylalkylamine N-acetyltransferase.
title_fullStr Acetyl group coordinated progression through the catalytic cycle of an arylalkylamine N-acetyltransferase.
title_full_unstemmed Acetyl group coordinated progression through the catalytic cycle of an arylalkylamine N-acetyltransferase.
title_sort acetyl group coordinated progression through the catalytic cycle of an arylalkylamine n-acetyltransferase.
publisher Public Library of Science (PLoS)
series PLoS ONE
issn 1932-6203
publishDate 2017-01-01
description The transfer of an acetyl group from acetyl-CoA to an acceptor amine is a ubiquitous biochemical transformation catalyzed by Gcn5-related N-acetyltransferases (GNATs). Although it is established that the reaction proceeds through a sequential ordered mechanism, the role of the acetyl group in driving the ordered formation of binary and ternary complexes remains elusive. Herein, we show that CoA and acetyl-CoA alter the conformation of the substrate binding site of an arylalkylamine N-acetyltransferase (AANAT) to facilitate interaction with acceptor substrates. However, it is the presence of the acetyl group within the catalytic funnel that triggers high affinity binding. Acetyl group occupancy is relayed through a conserved salt bridge between the P-loop and the acceptor binding site, and is manifested as differential dynamics in the CoA and acetyl-CoA-bound states. The capacity of the acetyl group carried by an acceptor to promote its tight binding even in the absence of CoA, but also its mutually exclusive position to the acetyl group of acetyl-CoA underscore its importance in coordinating the progression of the catalytic cycle.
url http://europepmc.org/articles/PMC5423648?pdf=render
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