PDBsum entry: 1mt6

Transferase

PDB id: 1mt6

Contents

Protein chain

280 a.a. *

Ligands

SAH

Waters ×171

* Residue conservation analysis

PDB id:

1mt6

Name:

Transferase

Title:

Structure of histone h3 k4-specific methyltransferase set7/9 with adohcy

Structure:

Set9. Chain: a. Synonym: histone h3 lysine 4 specific methyltransferase, set7/9. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.

Resolution:

2.20Å R-factor: 0.226 R-free: 0.263

Authors:

S.A.Jacobs,J.M.Harp,S.Devarakonda,Y.Kim,F.Rastinejad, S.Khorasanizadeh

Key ref:

S.A.Jacobs et al. (2002). The active site of the SET domain is constructed on a knot. Nat Struct Biol, 9, 833-838. PubMed id: 12389038 DOI: 10.1038/nsb861

Date:

20-Sep-02 Release date: 06-Nov-02

Protein chain

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

Seq: 366 a.a.

Struc: 280 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) corresponds exactly) + N(6)-methyl-L-lysine-[histone]

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

Added reference

DOI no: 10.1038/nsb861

Nat Struct Biol 9:833-838 (2002)

PubMed id: 12389038

The active site of the SET domain is constructed on a knot.

S.A.Jacobs, J.M.Harp, S.Devarakonda, Y.Kim, F.Rastinejad, S.Khorasanizadeh.

ABSTRACT

The SET domain contains the catalytic center of lysine methyltransferases that target the N-terminal tails of histones and regulate chromatin function. Here we report the structure of the SET7/9 protein in the absence and presence of its cofactor product, S-adenosyl-L-homocysteine (AdoHcy). A knot within the SET domain helps form the methyltransferase active site, where AdoHcy binds and lysine methylation is likely to occur. A structure-guided comparison of sequences within the SET protein family suggests that the knot substructure and active site environment are conserved features of the SET domain.

Selected figure(s)

Figure 2.
Figure 2. Three-dimensional structure of SET7/9. a, Stereo view of the overall fold of the nonconserved NTD (green), SET domain (blue and red) and the bound AdoHcy (yellow) prepared using Ribbons^34. The 'hoop' and 'thread' of the SET domain knot are red. b, Topology diagram of SET7/9. Secondary structure elements are colored as in (a). c, Stereo view of the electron density for the knot structure prepared using PyMOL (http://www.pymol.org). The |F[o] - F[c]| simulated annealing omit map contoured at 3 s, with residues 293−307 and 329−335 omitted for map calculation, depicts the hoop (blue) and thread (red) regions.

Figure 3.
Figure 3. SET7/9 binding to AdoHcy. a, Stereo view of the cofactor electron density in the pocket of SET7/9 prepared using PyMOL. An |F[o] - F[c]| simulated annealing omit map is contoured at 3 , with the AdoHcy molecule omitted for map calculation. Hydrogen bonds are represented with black dotted lines. Upon AdoHcy binding, Tyr 335 shifts (arrow) from the apo form (purple) to bring its OH group into the active site, and a water molecule binds near the sulfur atom of AdoHcy. b, Schematic LIGPLOT^35 depiction of the interactions between the SET domain and AdoHcy. Dashed lines represent hydrogen bonds, and arcs represent van der Waals interactions. c, Molecular surface of SET7/9 showing the AdoHcy binding pocket adjacent to the knot region. The putative site of the substrate epsilon amino group is shown as a white dot. Surface-exposed conserved residues (Fig. 4) are colored in green. The figure was prepared using GRASP^36.

The above figures are reprinted by permission from Macmillan Publishers Ltd: Nat Struct Biol (2002, 9, 833-838) copyright 2002.

Figures were selected by an automated process.