PDBsum entry: 1h3i

Transferase

PDB id: 1h3i

Contents

Protein chains

293 a.a. *

Metals

_MG ×3

Waters ×344

* Residue conservation analysis

PDB id:

1h3i

Name:

Transferase

Title:

Crystal structure of the histone methyltransferase set7/9

Structure:

Histone h3 lysine 4 specific methyltransferase. Chain: a, b. Fragment: n-domain, set-domain, residues 52-344. Synonym: histone h3-k4, methyltransferase. Engineered: yes

Source:

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

Biol. unit:

Monomer (from PDB file)

Resolution:

2.10Å R-factor: 0.212 R-free: 0.255

Authors:

J.R.Wilson,C.Jing,P.A.Walker,S.R.Martin,S.A.Howell, G.M.Blackburn,S.J.Gamblin,B.Xiao

Key ref:

J.R.Wilson et al. (2002). Crystal structure and functional analysis of the histone methyltransferase SET7/9. Cell, 111, 105-115. PubMed id: 12372304 DOI: 10.1016/S0092-8674(02)00964-9

Date:

04-Sep-02 Release date: 11-Nov-02

Protein chains

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

Seq: 366 a.a.

Struc: 293 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]

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

Added reference

DOI no: 10.1016/S0092-8674(02)00964-9

Cell 111:105-115 (2002)

PubMed id: 12372304

Crystal structure and functional analysis of the histone methyltransferase SET7/9.

J.R.Wilson, C.Jing, P.A.Walker, S.R.Martin, S.A.Howell, G.M.Blackburn, S.J.Gamblin, B.Xiao.

ABSTRACT

Methylation of lysine residues in the N-terminal tails of histones is thought to represent an important component of the mechanism that regulates chromatin structure. The evolutionarily conserved SET domain occurs in most proteins known to possess histone lysine methyltransferase activity. We present here the crystal structure of a large fragment of human SET7/9 that contains a N-terminal beta-sheet domain as well as the conserved SET domain. Mutagenesis identifies two residues in the C terminus of the protein that appear essential for catalytic activity toward lysine-4 of histone H3. Furthermore, we show how the cofactor AdoMet binds to this domain and present biochemical data supporting the role of invariant residues in catalysis, binding of AdoMet, and interactions with the peptide substrate.

Selected figure(s)

Figure 1.
Figure 1. The Structure of SET7/9(A) Two orthogonal views of the structure are shown in ribbon representation. The N domain (residues 52–192) is colored green, the loop connecting the N domain with the conserved core of the SET domain is colored blue, and the SET domain is colored yellow. The secondary structure elements are labeled.(B) A stereographic representation of the Cα trace of the SET domain colored and oriented as the right-hand panel of (A); every 20^th residue is labeled.(C) Schematic representation of the topology of the SET domain colored as in (A). β-strands are shown as triangles and helical segments as circles, the N terminus of the SET domain (residue 193) is indicated by an open circle, and the last residue in the crystal structure (344) by the solid arrowhead. The C terminus forms a threaded loop through the central 3[10]-β20 connection.(D) The molecular surface of the N domain of SET7/9 is colored according to its electrostatic potential as calculated using GRASP. Negative electrostatic potential is red, with positive electrostatic potential blue. The molecule is oriented as in the left panel of (A).

Figure 2.
Figure 2. Conservation of Residues across the SET Family(A) Sequence alignment of SET7/9 with a subset of other SET domains. The entire coding sequence of SET7/9 is shown together with the secondary structure elements assigned from the crystal structure, colored according to Figure 1A. The aligned sequences are from PR-Set07 (AAF97812), human G9a (S30385), human SUV39H1 (NP003164), and set2 (NP012367). The sequences were aligned using Clustalw. Residues invariant across these domains are boxed in blue, while two conservatively substituted residues are boxed in light blue. The extent of the crystal structure is indicated by the red line.(B) Surface representation of SET domain with conserved residues colored according to (A) with the three conserved regions labeled.

The above figures are reprinted by permission from Cell Press: Cell (2002, 111, 105-115) copyright 2002.

Figures were selected by an automated process.