5EG2

SET7/9 N265A in complex with AdoHcy and TAF10 peptide

Summary for 5EG2

• Entry DOI: 10.2210/pdb5eg2/pdb
• Descriptor: Histone-lysine N-methyltransferase SETD7, Transcription initiation factor TFIID subunit 10, S-ADENOSYL-L-HOMOCYSTEINE, ... (5 entities in total)
• Functional Keywords: transferase-transcription factor complex, transferase/transcription factor
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 2
• Total formula weight: 30737.23

Authors

Kroner, G.M.,Fick, R.J.,Trievel, R.C. (deposition date: 2015-10-26, release date: 2016-01-13, Last modification date: 2023-09-27)

Primary citation

Fick, R.J.,Kroner, G.M.,Nepal, B.,Magnani, R.,Horowitz, S.,Houtz, R.L.,Scheiner, S.,Trievel, R.C.
Sulfur-Oxygen Chalcogen Bonding Mediates AdoMet Recognition in the Lysine Methyltransferase SET7/9.
Acs Chem.Biol., 11:748-754, 2016

PubMed Abstract: Recent studies have demonstrated that carbon-oxygen (CH···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···O) chalcogen bonds in which the oxygen atom donates a lone pair of electrons to the σ 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···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···O chalcogen bonds relative to their neutral thioether counterparts. An inspection of high-resolution crystal structures reveals the presence of AdoMet S···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···O chalcogen bonds contribute to AdoMet recognition and can enable methyltransferases to distinguish between substrate and product.

PubMed: 26713889
DOI: 10.1021/acschembio.5b00852

Experimental method

X-RAY DIFFRACTION (1.55 Å)