3RIB

Human lysine methyltransferase Smyd2 in complex with AdoHcy

Summary for 3RIB

• Entry DOI: 10.2210/pdb3rib/pdb
• Descriptor: N-lysine methyltransferase SMYD2, ZINC ION, S-ADENOSYL-L-HOMOCYSTEINE, ... (5 entities in total)
• Functional Keywords: smyd proteins, mynd, set domain, histone lysine methyltransferase, histone methylation, h3k36, h3k4, transferase
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm, cytosol : Q9NRG4
• Total number of polymer chains: 2
• Total formula weight: 103688.33

Authors

Xu, S.,Zhang, T.,Zhong, C.,Ding, J. (deposition date: 2011-04-13, release date: 2011-07-20, Last modification date: 2024-03-20)

Primary citation

Xu, S.,Zhong, C.,Zhang, T.,Ding, J.
Structure of human lysine methyltransferase Smyd2 reveals insights into the substrate divergence in Smyd proteins
J Mol Cell Biol, 3:293-300, 2011

PubMed Abstract: The SET- and myeloid-Nervy-DEAF-1 (MYND)-domain containing (Smyd) lysine methyltransferases 1-3 share relatively high sequence similarity but exhibit divergence in the substrate specificity. Here we report the crystal structure of the full-length human Smyd2 in complex with S-adenosyl-L-homocysteine (AdoHcy). Although the Smyd1-3 enzymes are similar in the overall structure, detailed comparisons demonstrate that they differ substantially in the potential substrate-binding site. The binding site of Smyd3 consists mainly of a deep and narrow pocket, while those of Smyd1 and Smyd2 consist of a comparable pocket and a long groove. In addition, Smyd2, which has lysine methyltransferase activity on histone H3-lysine 36, exhibits substantial differences in the wall of the substrate-binding pocket compared with those of Smyd1 and Smyd3 which have activity specifically on histone H3-lysine 4. The differences in the substrate-binding site might account for the observed divergence in the specificity and methylation state of the substrates. Further modeling study of Smyd2 in complex with a p53 peptide indicates that mono-methylation of p53-Lys(372) might result in steric conflict of the methyl group with the surrounding residues of Smyd2, providing a structural explanation for the inhibitory effect of the SET7/9-mediated mono-methylation of p53-Lys(372) on the Smyd2-mediated methylation of p53-Lys(370).

PubMed: 21724641
DOI: 10.1093/jmcb/mjr015

Experimental method

X-RAY DIFFRACTION (2.79 Å)