Restriction of S-adenosylmethionine conformational freedom by knotted protein binding sites.
Adenine
/ chemistry
Amino Acid Motifs
Binding Sites
Computational Biology
/ methods
Computer Simulation
Databases, Protein
Glycine
/ chemistry
Magnetic Resonance Spectroscopy
Methionine Adenosyltransferase
/ chemistry
Molecular Dynamics Simulation
Principal Component Analysis
Protein Binding
Protein Domains
Protein Folding
S-Adenosylmethionine
/ chemistry
Solvents
Temperature
Water
/ chemistry
tRNA Methyltransferases
/ chemistry
Journal
PLoS computational biology
ISSN: 1553-7358
Titre abrégé: PLoS Comput Biol
Pays: United States
ID NLM: 101238922
Informations de publication
Date de publication:
05 2020
05 2020
Historique:
received:
07
10
2019
accepted:
23
04
2020
revised:
26
06
2020
pubmed:
27
5
2020
medline:
8
8
2020
entrez:
27
5
2020
Statut:
epublish
Résumé
S-adenosylmethionine (SAM) is one of the most important enzyme substrates. It is vital for the function of various proteins, including large group of methyltransferases (MTs). Intriguingly, some bacterial and eukaryotic MTs, while catalysing the same reaction, possess significantly different topologies, with the former being a knotted one. Here, we conducted a comprehensive analysis of SAM conformational space and factors that affect its vastness. We investigated SAM in two forms: free in water (via NMR studies and explicit solvent simulations) and bound to proteins (based on all data available in the PDB and on all-atom molecular dynamics simulations in water). We identified structural descriptors-angles which show the major differences in SAM conformation between unknotted and knotted methyltransferases. Moreover, we report that this is caused mainly by a characteristic for knotted MTs compact binding site formed by the knot and the presence of adenine-binding loop. Additionally, we elucidate conformational restrictions imposed on SAM molecules by other protein groups in comparison to conformational space in water.
Identifiants
pubmed: 32453784
doi: 10.1371/journal.pcbi.1007904
pii: PCOMPBIOL-D-19-01715
pmc: PMC7319350
doi:
Substances chimiques
Solvents
0
Water
059QF0KO0R
S-Adenosylmethionine
7LP2MPO46S
tRNA Methyltransferases
EC 2.1.1.-
Methionine Adenosyltransferase
EC 2.5.1.6
Adenine
JAC85A2161
Glycine
TE7660XO1C
Banques de données
figshare
['10.6084/m9.figshare.9944423']
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1007904Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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