Document Type
Article
Journal/Book Title
Molecules
Publication Date
11-13-2018
Publisher
MDPI
Volume
23
Issue
11
First Page
1
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
Last Page
17
Abstract
Tetrel bonds represent a category of non-bonding interaction wherein an electronegative atom donates a lone pair of electrons into the sigma antibonding orbital of an atom in the carbon group of the periodic table. Prior computational studies have implicated tetrel bonding in the stabilization of a preliminary state that precedes the transition state in SN2 reactions, including methyl transfer. Notably, the angles between the tetrel bond donor and acceptor atoms coincide with the prerequisite geometry for the SN2 reaction. Prompted by these findings, we surveyed crystal structures of methyltransferases in the Protein Data Bank and discovered multiple instances of carbon tetrel bonding between the methyl group of the substrate S-adenosylmethionine (AdoMet) and electronegative atoms of small molecule inhibitors, ions, and solvent molecules. The majority of these interactions involve oxygen atoms as the Lewis base, with the exception of one structure in which a chlorine atom of an inhibitor functions as the electron donor. Quantum mechanical analyses of a representative subset of the methyltransferase structures from the survey revealed that the calculated interaction energies and spectral properties are consistent with the values for bona fide carbon tetrel bonds. The discovery of methyl tetrel bonding offers new insights into the mechanism underlying the SN2 reaction catalyzed by AdoMet-dependent methyltransferases. These findings highlight the potential of exploiting these interactions in developing new methyltransferase inhibitors.
Recommended Citation
Trievel, R.C.; Scheiner, S. Crystallographic and Computational Characterization of Methyl Tetrel Bonding in S-Adenosylmethionine-Dependent Methyltransferases. Molecules 2018, 23, 2965.
