1PEG

Structural basis for the product specificity of histone lysine methyltransferases

Summary for 1PEG

• Entry DOI: 10.2210/pdb1peg/pdb
• Related: 1ML9
• Descriptor: histone H3 methyltransferase DIM-5, Histone H3, ZINC ION, ... (4 entities in total)
• Functional Keywords: ternary structure of dim-5, a suv39-type histone-h3 lys-9 methyltransferase, set domain protein forms a knot-like substructure, pre-set triangular zn3cys9 zinc cluster, post-set zinc-binding site, a hybrid beta sheet formed by dim-5 and h3 tail, transferase
• Biological source: Neurospora crassa; More
• Cellular location: Nucleus (By similarity): Q8X225; Nucleus: P02303
• Total number of polymer chains: 4
• Total formula weight: 72646.79

Authors

Zhang, X.,Yang, Z.,Khan, S.I.,Horton, J.R.,Tamaru, H.,Selker, E.U.,Cheng, X. (deposition date: 2003-05-21, release date: 2003-08-05, Last modification date: 2023-08-16)

Primary citation

Zhang, X.,Yang, Z.,Khan, S.I.,Horton, J.R.,Tamaru, H.,Selker, E.U.,Cheng, X.
Structural basis for the product specificity of histone lysine methyltransferases
Mol.Cell, 12:177-185, 2003

PubMed 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.

PubMed: 12887903
DOI: 10.1016/S1097-2765(03)00224-7

Experimental method

X-RAY DIFFRACTION (2.59 Å)