Restriction of S-adenosylmethionine conformational freedom by knotted protein binding sites

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 topolog...

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Bibliographic Details
Published in:PLoS computational biology 2020-05, Vol.16 (5), p.e1007904-e1007904
Main Authors: Perlinska, Agata P, Stasiulewicz, Adam, Nawrocka, Ewa K, Kazimierczuk, Krzysztof, Setny, Piotr, Sulkowska, Joanna I
Format: Article
Language:English
Subjects:
Adenine
Adenosylmethionine
Amino acids
Antibiotics
Binding sites
Binding sites (Biochemistry)
Biology and Life Sciences
Ligands
Molecular dynamics
NMR
Nuclear magnetic resonance
Observations
Physical Sciences
Physiological aspects
Protein binding
Protein conformation
Protein research
Proteins
Research and Analysis Methods
S-Adenosylmethionine
Substrates
Substrates (Biochemistry)
Topology
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Summary: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.
ISSN:1553-7358
1553-734X
1553-7358
DOI:10.1371/journal.pcbi.1007904