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Structural basis for the product specificity of histone lysine methyltransferases

OverviewOverview

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.

About this StructureAbout this Structure

1PEG is a Protein complex structure of sequences from Neurospora crassa. Full crystallographic information is available from OCA.

ReferenceReference

Structural basis for the product specificity of histone lysine methyltransferases., Zhang X, Yang Z, Khan SI, Horton JR, Tamaru H, Selker EU, Cheng X, Mol Cell. 2003 Jul;12(1):177-85. PMID:12887903 Page seeded by OCA on Sat May 3 04:59:39 2008