1O9S: Crystal Structure of a Ternary Complex of the Human Histone Methyltransferase Set79

Acetylation, phosphorylation and methylation of the amino-terminal tails of histones are thought to be involved in the regulation of chromatin structure and function. With just one exception, the enzymes identified in the methylation of specific lysine residues on histones (histone methyltransferases) belong to the SET family. The high-resolution crystal structure of a ternary complex of human SET7/9 with a histone peptide and cofactor reveals that the peptide substrate and cofactor bind on opposite surfaces of the enzyme. The target lysine accesses the active site of the enzyme and the S-adenosyl-l-methionine (AdoMet) cofactor by inserting its side chain into a narrow channel that runs through the enzyme, connecting the two surfaces. Here we show from the structure and from solution studies that SET7/9, unlike most other SET proteins, is exclusively a mono-methylase. The structure indicates the molecular basis of the specificity of the enzyme for the histone target, and allows us to propose a model for the methylation reaction that accounts for the role of many of the residues that are invariant across the SET family.
PDB ID: 1O9SDownload
MMDB ID: 22218
PDB Deposition Date: 2002/12/18
Updated in MMDB: 2012/10 
Experimental Method:
x-ray diffraction
Resolution: 1.75  Å
Source Organism:
Similar Structures:
Biological Unit for 1O9S: dimeric; determined by author and by software (PQS)
Molecular Components in 1O9S
Label Count Molecule
Proteins (2 molecules)
Histone-lysine N-methyltransferase, H3 Lysine-4 Specific
(Gene: SETD7)
Molecule annotation
Gene Fragment for Histone H3
Molecule annotation
Chemical (1 molecule)
* Click molecule labels to explore molecular sequence information.

Citing MMDB