PDBsum entry: 1o9s

Transferase

PDB id: 1o9s

Contents

Protein chains

250 a.a. *

Ligands

ALA-ARG-THR-MLZ-GLN-THR-ALA-ARG-LYS-TYR

ALA-ARG-THR-MLZ-GLN-THR

SAH ×2

Waters ×660

* Residue conservation analysis

PDB id:

1o9s

Name:

Transferase

Title:

Crystal structure of a ternary complex of the human histone methyltransferase set7/9

Structure:

Histone-lysine n-methyltransferase, h3 lysine-4 specific. Chain: a, b. Fragment: n-domain, set-domain, residues 108-366. Synonym: histone h3-k4 methyltransferase, h3-k4-hmtase. Engineered: yes. Gene fragment for histone h3. Chain: k, l. Fragment: residues 2-11

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes. Organism_taxid: 9606

Biol. unit:

Dimer (from PDB file)

Resolution:

1.75Å R-factor: 0.206 R-free: 0.222

Authors:

B.Xiao,C.Jing,J.R.Wilson,P.A.Walker,N.Vasisht,G.Kelly, S.Howell,I.A.Taylor,G.M.Blackburn,S.J.Gamblin

Key ref:

B.Xiao et al. (2003). Structure and catalytic mechanism of the human histone methyltransferase SET7/9. Nature, 421, 652-656. PubMed id: 12540855 DOI: 10.1038/nature01378

Date:

18-Dec-02 Release date: 06-Feb-03

Protein chains

Q8WTS6  (SETD7_HUMAN) -  Histone-lysine N-methyltransferase SETD7

Seq: 366 a.a.

Struc: 250 a.a.

Enzyme reactions

• Enzyme class: E.C.2.1.1.43 - Histone-lysine N-methyltransferase.
• Reaction: S-adenosyl-L-methionine + L-lysine-[histone] = S-adenosyl-L-homocysteine + N₆-methyl-L-lysine-[histone]

S-adenosyl-L-methionine + L-lysine-[histone] = S-adenosyl-L-homocysteine (Bound ligand (Het Group name = SAH) matches with 96.00% similarity) + N(6)-methyl-L-lysine-[histone]

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

Added reference

DOI no: 10.1038/nature01378

Nature 421:652-656 (2003)

PubMed id: 12540855

Structure and catalytic mechanism of the human histone methyltransferase SET7/9.

B.Xiao, C.Jing, J.R.Wilson, P.A.Walker, N.Vasisht, G.Kelly, S.Howell, I.A.Taylor, G.M.Blackburn, S.J.Gamblin.

ABSTRACT

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.

Selected figure(s)

Figure 1.
Figure 1: Structure of the SET7/9 ternary complex. a, Two orthogonal views of the SET7/9 ternary complex in ribbons representation. The N-terminal domain is coloured pink, the SET domain is blue and the C-terminal segment is grey. The H3 peptide is indicated in green, with the side chain of methylated Lys 4 shown. The S-adenosyl-l-homocysteine (AdoHcy) cofactor is coloured yellow. The secondary structure elements are labelled according to our earlier structure. Two small turns of the 3[10] helix are also labelled. b, Two views of the SET domain are shown in a surface representation coloured according to electrostatic potential (the two views are related by a twofold rotation about a vertical axis). The left panel shows AdoHcy coloured yellow; the right panel shows the H3 peptide coloured green. The inset panel shows a close-up view of the lysine access channel containing the methyl lysine side chain as viewed from the S-adenosyl-l-methionine (AdoMet)-binding site.

Figure 4.
Figure 4: Peptide interactions with SET7/9. a, Schematic representation of interactions made by the histone H3 peptide in complex with SET7/9. The positions of residues beyond the +1 position are not shown because they are affected by lattice contacts. b, Sequences of histones subject to methylation, aligned according to the position of their target lysine residues. Basic residues are highlighted in red.

The above figures are reprinted by permission from Macmillan Publishers Ltd: Nature (2003, 421, 652-656) copyright 2003.

Figures were selected by the author.