1PEG: Structural Basis For The Product Specificity Of Histone Lysine Methyltransferases

Citation:
Abstract
DIM-5 is a SUV39-type histone H3 Lys9 methyltransferase that is essential for DNA methylation in N. crassa. We report the structure of a ternary complex including DIM-5, S-adenosyl-L-homocysteine, and a substrate H3 peptide. The histone tail inserts as a parallel strand between two DIM-5 strands, completing a hybrid sheet. Three post-SET cysteines coordinate a zinc atom together with Cys242 from the SET signature motif (NHXCXPN) near the active site. Consequently, a narrow channel is formed to accommodate the target Lys9 side chain. The sulfur atom of S-adenosyl-L-homocysteine, where the transferable methyl group is to be attached in S-adenosyl-L-methionine, lies at the opposite end of the channel, approximately 4 A away from the target Lys9 nitrogen. Structural comparison of the active sites of DIM-5, an H3 Lys9 trimethyltransferase, and SET7/9, an H3 Lys4 monomethyltransferase, allowed us to design substitutions in both enzymes that profoundly alter their product specificities without affecting their catalytic activities.
PDB ID: 1PEGDownload
MMDB ID: 24257
PDB Deposition Date: 2003/5/21
Updated in MMDB: 2012/10
Experimental Method:
x-ray diffraction
Resolution: 2.59  Å
Source Organism:
synthetic construct
Similar Structures:
Biological Unit for 1PEG: dimeric; determined by author
Molecular Components in 1PEG
Label Count Molecule
Proteins (2 molecules)
1
Histone H3 Methyltransferase Dim-5(Gene symbol: dim-5)
Molecule annotation
1
Histone H3
Molecule annotation
Chemicals (5 molecules)
1
4
2
1
* Click molecule labels to explore molecular sequence information.

Citing MMDB
.