PDBsum entry 2p5b

Metal binding protein

PDB id: 2p5b

Contents

Protein chains

347 a.a. *

17 a.a. *

14 a.a. *

Ligands

OGA ×2

OXY ×3

Metals

_ZN ×2

FE2 ×2

Waters ×284

* Residue conservation analysis

PDB id:

2p5b

Name:

Metal binding protein

Title:

The complex structure of jmjd2a and trimethylated h3k36 peptide

Structure:

Jmjc domain-containing histone demethylation protein 3a. Chain: a, b. Fragment: catalytic core. Synonym: jumonji domain-containing protein 2a. Engineered: yes. Histone h3. Chain: i, j. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: jmjd2a, jhdm3a, jmjd2, kiaa0677. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes

Resolution:

1.99Å R-factor: 0.238 R-free: 0.263

Authors:

G.Zhang,Z.Chen,J.Zang,X.Hong,Y.Shi

Key ref:

Z.Chen et al. (2007). Structural basis of the recognition of a methylated histone tail by JMJD2A. Proc Natl Acad Sci U S A, 104, 10818-10823. PubMed id: 17567753 DOI: 10.1073/pnas.0704525104

Date:

14-Mar-07 Release date: 12-Jun-07

Protein chains

O75164  (KDM4A_HUMAN) -  Lysine-specific demethylase 4A from Homo sapiens

Seq: 1064 a.a.

Struc: 347 a.a.

Protein chain

P84239  (H3_URECA) -  Histone H3 from Urechis caupo

Seq: 136 a.a.

Struc: 17 a.a.*

Protein chain

P84239  (H3_URECA) -  Histone H3 from Urechis caupo

Seq: 136 a.a.

Struc: 14 a.a.*

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

Enzyme reactions

• Enzyme class 2: Chains A, B: E.C.1.14.11.66 - [histone H3]-trimethyl-L-lysine(9) demethylase.
• Reaction: N₆,N₆,N₆-trimethyl-L-lysyl₉-[histone H3] + 2 2-oxoglutarate + 2 O2 = N₆-methyl-L-lysyl₉-[histone H3] + 2 formaldehyde + 2 succinate + 2 CO2

N(6),N(6),N(6)-trimethyl-L-lysyl(9)-[histone H3] + 2 × 2-oxoglutarate + 2 × O2 (Bound ligand (Het Group name = OXY) corresponds exactly) = N(6)-methyl-L-lysyl(9)-[histone H3] + 2 × formaldehyde + 2 × succinate + 2 × CO2

• Enzyme class 3: Chains A, B: E.C.1.14.11.69 - [histone H3]-trimethyl-L-lysine(36) demethylase.
• Reaction: N₆,N₆,N₆-trimethyl-L-lysyl₃₆-[histone H3] + 2 2-oxoglutarate + 2 O2 = N₆-methyl-L-lysyl₃₆-[histone H3] + 2 formaldehyde + 2 succinate + 2 CO2

N(6),N(6),N(6)-trimethyl-L-lysyl(36)-[histone H3] + 2 × 2-oxoglutarate + 2 × O2 (Bound ligand (Het Group name = OXY) corresponds exactly) = N(6)-methyl-L-lysyl(36)-[histone H3] + 2 × formaldehyde + 2 × succinate + 2 × CO2

Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.

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

reference

DOI no: 10.1073/pnas.0704525104

Proc Natl Acad Sci U S A 104:10818-10823 (2007)

PubMed id: 17567753

Structural basis of the recognition of a methylated histone tail by JMJD2A.

Z.Chen, J.Zang, J.Kappler, X.Hong, F.Crawford, Q.Wang, F.Lan, C.Jiang, J.Whetstine, S.Dai, K.Hansen, Y.Shi, G.Zhang.

ABSTRACT

The Jumonji C domain is a catalytic motif that mediates histone lysine demethylation. The Jumonji C-containing oxygenase JMJD2A specifically demethylates tri- and dimethylated lysine-9 and lysine-36 of histone 3 (H3K9/36 me3/2). Here we present structures of the JMJD2A catalytic core complexed with methylated H3K36 peptide substrates in the presence of Fe(II) and N-oxalylglycine. We found that the interaction between JMJD2A and peptides largely involves the main chains of the enzyme and the peptide. The peptide-binding specificity is primarily determined by the primary structure of the peptide, which explains the specificity of JMJD2A for methylated H3K9 and H3K36 instead of other methylated residues such as H3K27. The specificity for a particular methyl group, however, is affected by multiple factors, such as space and the electrostatic environment in the catalytic center of the enzyme. These results provide insights into the mechanisms and specificity of histone demethylation.

Selected figure(s)

Figure 1.
Fig. 1. The overall complex structure of c-JMJD2A with the H3K36me3 peptide in the presence of NOG (orange), Fe(II) (pink), and Zn (purple). (A) c-JMJD2A is shown as a ribbon model with the Jumonji N domain (green), the long hairpin (purple), the mixed structural motif (gray), the Jumonji C domain (light blue), the C-terminal domain (pink), and the methylated H3K36 peptide (yellow). Seventeen of the 22 residues (residues 27–43 from histone 3) of the methylated peptide are ordered in the structure (molecule A). (B) A stick and ball model of the peptide on the surface of c-JMJD2A colored according to the electrostatic potential of the residues (red and blue represent negatively and positively charged areas, respectively). All structural figures were made by using the PyMOL program (http://pymol.sourceforge.net).

Figure 2.
Fig. 2. The detailed interaction between c-JMJD2A and the methylated peptides. (A) A schematic view of all of the potential interactions between c-JMJD2A and the H3K36 peptide, including 10 hydrogen bonds and one salt bridge. (B) Mutagenesis data and activity assays. Residues Q86, N88, D135, and Y175 are involved in the interaction with the peptide, whereas residues Y177, N290, S288, and T289 are involved in methyl group binding. K241 is proposed to recruit the O[2] molecule into the catalytic center. (C) Characterization of the binding between the H3K36 peptide and c-JMJD2A. (D) Characterization of the binding between of the H3K9 peptide and c-JMJD2A. Neither of the binding curves is linear, suggesting that the peptides assume multiple conformations.

Figures were selected by an automated process.