Journal article
Sulfur-Oxygen Chalcogen Bonding Mediates AdoMet Recognition in the Lysine Methyltransferase SET7/9
ACS chemical biology, v 11(3), pp 748-754
18 Mar 2016
PMID: 26713889
Abstract
Recent studies have demonstrated that carbon-oxygen (CH center dot center dot center dot O) hydrogen bonds have important roles in S-adenosylmethionine (AdoMet) recognition and catalysis in methyltransferases. Here, we investigate noncovalent interactions that occur between the AdoMet sulfur cation and oxygen atoms in methyltransferase active sites. These interactions represent sulfur oxygen (S center dot center dot center dot O) chalcogen bonds in which the oxygen atom donates a lone pair of electrons to the sigma antibonding orbital of the AdoMet sulfur atom. Structural, biochemical,. and computational analyses of an asparagine mutation in the lysine methyltransferase SET7/9 that abolishes AdoMet S center dot center dot center dot O chalcogen bonding reveal that this interaction enhances substrate binding affinity relative to the product S-adenosylhomocysteine. Corroborative quantum mechanical calculations demonstrate that sulfonium systems form strong S center dot center dot center dot O chalcogen bonds relative to their neutral thioether counterparts. An inspection of high-resolution crystal structures reveals the presence of AdoMet S center dot center dot center dot O chalcogen bonding in different classes of methyltransferases, illustrating that these interactions are not limited to SET domain methyltransferases. Together, these results demonstrate that S center dot center dot center dot O chalcogen bonds contribute to AdoMet recognition and can enable methyltransferases to distinguish between substrate and product.
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Details
- Title
- Sulfur-Oxygen Chalcogen Bonding Mediates AdoMet Recognition in the Lysine Methyltransferase SET7/9
- Creators
- Robert J. Fick - Univ Michigan, Dept Biol Chem, Ann Arbor, MI 48109 USAGrace M. Kroner - Univ Michigan, Dept Biol Chem, Ann Arbor, MI 48109 USABinod Nepal - Utah State UniversityRoberta Magnani - University of KentuckyScott Horowitz - Howard Hughes Medical InstituteRobert L. Houtz - University of KentuckySteve Scheiner - Utah State UniversityRaymond C. Trievel - Univ Michigan, Dept Biol Chem, Ann Arbor, MI 48109 USAArgonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
- Publication Details
- ACS chemical biology, v 11(3), pp 748-754
- Publisher
- Amer Chemical Soc
- Number of pages
- 7
- Grant note
- 085P1000817 / Michigan Technology Tri-Corridor DE-AC02-06CH11357 / U.S. DOE; United States Department of Energy (DOE) Michigan Economic Development Corporation 1508492 / Division Of Chemistry; National Science Foundation (NSF); NSF - Directorate for Mathematical & Physical Sciences (MPS)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Microbiology and Immunology
- Web of Science ID
- WOS:000372664800022
- Scopus ID
- 2-s2.0-84961839379
- Other Identifier
- 991021955788304721
InCites Highlights
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology