3RIB: Human lysine methyltransferase Smyd2 in complex with AdoHcy

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).
PDB ID: 3RIBDownload
MMDB ID: 92198
PDB Deposition Date: 2011/4/13
Updated in MMDB: 2017/11
Experimental Method:
x-ray diffraction
Resolution: 2.79  Å
Source Organism:
Similar Structures:
Biological Unit for 3RIB: monomeric; determined by author and by software (PISA)
Molecular Components in 3RIB
Label Count Molecule
Protein (1 molecule)
N-lysine Methyltransferase Smyd2(Gene symbol: SMYD2)
Molecule annotation
Chemicals (11 molecules)
* Click molecule labels to explore molecular sequence information.

Citing MMDB