1N6C

Structure of SET7/9

Summary for 1N6C

• Entry DOI: 10.2210/pdb1n6c/pdb
• Related: 1N6A
• Descriptor: SET domain-containing protein 7, S-ADENOSYLMETHIONINE (3 entities in total)
• Functional Keywords: protein-ligand complex, transferase
• Biological source: Homo sapiens (human)
• Cellular location: Nucleus: Q8WTS6
• Total number of polymer chains: 1
• Total formula weight: 33420.93

Authors

Kwon, T.W.,Chang, J.H.,Cho, Y. (deposition date: 2002-11-09, release date: 2003-02-04, Last modification date: 2024-03-13)

Primary citation

Kwon, T.,Chang, J.H.,Kwak, E.,Lee, C.W.,Joachimiak, A.,Kim, Y.C.,Lee, J.,Cho, Y.
Mechanism of histone lysine methyl transfer revealed by the structure of SET7/9-AdoMet
EMBO J., 22:292-303, 2003

PubMed Abstract: The methylation of lysine residues of histones plays a pivotal role in the regulation of chromatin structure and gene expression. Here, we report two crystal structures of SET7/9, a histone methyltransferase (HMTase) that transfers methyl groups to Lys4 of histone H3, in complex with S-adenosyl-L-methionine (AdoMet) determined at 1.7 and 2.3 A resolution. The structures reveal an active site consisting of: (i) a binding pocket between the SET domain and a c-SET helix where an AdoMet molecule in an unusual conformation binds; (ii) a narrow substrate-specific channel that only unmethylated lysine residues can access; and (iii) a catalytic tyrosine residue. The methyl group of AdoMet is directed to the narrow channel where a substrate lysine enters from the opposite side. We demonstrate that SET7/9 can transfer two but not three methyl groups to unmodified Lys4 of H3 without substrate dissociation. The unusual features of the SET domain-containing HMTase discriminate between the un- and methylated lysine substrate, and the methylation sites for the histone H3 tail.

PubMed: 12514135
DOI: 10.1093/emboj/cdg025

Experimental method

X-RAY DIFFRACTION (2.3 Å)