PDBsum entry 2qqr

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Oxidoreductase PDB id
Jmol PyMol
Protein chain
118 a.a. *
SO4 ×6
Waters ×321
* Residue conservation analysis
PDB id:
Name: Oxidoreductase
Title: Jmjd2a hybrid tudor domains
Structure: Jmjc domain-containing histone demethylation protein 3a. Chain: a, b. Fragment: hybrid tudor domains (residues: 897-1011). Synonym: jumonji domain-containing protein 2a. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: jmjd2a, jhdm3a, jmjd2, kiaa0677. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
1.80Å     R-factor:   0.184     R-free:   0.213
Authors: J.Lee,M.V.Botuyan,G.Mer
Key ref:
J.Lee et al. (2008). Distinct binding modes specify the recognition of methylated histones H3K4 and H4K20 by JMJD2A-tudor. Nat Struct Biol, 15, 109-111. PubMed id: 18084306 DOI: 10.1038/nsmb1326
26-Jul-07     Release date:   11-Dec-07    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
O75164  (KDM4A_HUMAN) -  Lysine-specific demethylase 4A
1064 a.a.
118 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 2 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class: E.C.1.14.11.-  - ?????
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]


DOI no: 10.1038/nsmb1326 Nat Struct Biol 15:109-111 (2008)
PubMed id: 18084306  
Distinct binding modes specify the recognition of methylated histones H3K4 and H4K20 by JMJD2A-tudor.
J.Lee, J.R.Thompson, M.V.Botuyan, G.Mer.
The lysine demethylase JMJD2A has the unique property of binding trimethylated peptides from two different histone sequences (H3K4me3 and H4K20me3) through its tudor domains. Here we show using X-ray crystallography and calorimetry that H3K4me3 and H4K20me3, which are recognized with similar affinities by JMJD2A, adopt radically different binding modes, to the extent that we were able to design single point mutations in JMJD2A that inhibited the recognition of H3K4me3 but not H4K20me3 and vice versa.
  Selected figure(s)  
Figure 1.
(a) ITC of JMJD2A-tudor with H4K20me3 (left) and with H3K4me3 (right). The peptide amino acid sequences are indicated with the methylated (^*) lysine in red. Raw titration data and integrated heat measurements are shown in the upper and lower plots, respectively. The K[d] and stoichiometry numbers (n) obtained by fitting a standard one-interaction-site model are reported with the associated s.d. determined by nonlinear least-squares analysis. (b) Molecular surface and electrostatic potential representation of JMJD2A-tudor in complex with the H4K20me3 peptide. The electrostatic potential is shown in red for negatively charged and blue for positively charged surfaces. The peptide is in stick representation with the 2F[o] – F[c] electron density map displayed at the 1.0 contour level.
Figure 2.
(a,b) Close-up views of the JMJD2A-tudor interaction sites with H3K4me3 (a, PDB 2GFA^6) and H4K20me3 (b). Amino acids of JMJD2A-tudor involved in binding H3K4me3 and H4K20me3 are shown. (c) Overall view of JMJD2A-tudor in complex with superimposed H3K4me3 (pink) and H4K20me3 (green), illustrating the opposite orientations of these peptides.
  The above figures are reprinted from an Open Access publication published by Macmillan Publishers Ltd: Nat Struct Biol (2008, 15, 109-111) copyright 2008.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
23211769 C.A.Musselman, M.E.Lalonde, J.Côté, and T.G.Kutateladze (2012).
Perceiving the epigenetic landscape through histone readers.
  Nat Struct Mol Biol, 19, 1218-1227.  
23142980 C.A.Musselman, N.Avvakumov, R.Watanabe, C.G.Abraham, M.E.Lalonde, Z.Hong, C.Allen, S.Roy, J.K.Nuñez, J.Nickoloff, C.A.Kulesza, A.Yasui, J.Côté, and T.G.Kutateladze (2012).
Molecular basis for H3K36me3 recognition by the Tudor domain of PHF1.
  Nat Struct Mol Biol, 19, 1266-1272.
PDB code: 4hcz
23104054 C.Ballaré, M.Lange, A.Lapinaite, G.M.Martin, L.Morey, G.Pascual, R.Liefke, B.Simon, Y.Shi, O.Gozani, T.Carlomagno, S.A.Benitah, and L.Di Croce (2012).
Phf19 links methylated Lys36 of histone H3 to regulation of Polycomb activity.
  Nat Struct Mol Biol, 19, 1257-1265.
PDB code: 4bd3
22864287 G.Cui, S.Park, A.I.Badeaux, D.Kim, J.Lee, J.R.Thompson, F.Yan, S.Kaneko, Z.Yuan, M.V.Botuyan, M.T.Bedford, J.Q.Cheng, and G.Mer (2012).
PHF20 is an effector protein of p53 double lysine methylation that stabilizes and activates p53.
  Nat Struct Mol Biol, 19, 916-924.
PDB codes: 2ldm 3p8d 3sd4
  21141727 A.K.Upadhyay, and X.Cheng (2011).
Dynamics of histone lysine methylation: structures of methyl writers and erasers.
  Prog Drug Res, 67, 107-124.  
21193996 A.Kaldis, D.Tsementzi, O.Tanriverdi, and K.E.Vlachonasios (2011).
Arabidopsis thaliana transcriptional co-activators ADA2b and SGF29a are implicated in salt stress responses.
  Planta, 233, 749-762.  
22120668 K.Acs, M.S.Luijsterburg, L.Ackermann, F.A.Salomons, T.Hoppe, and N.P.Dantuma (2011).
The AAA-ATPase VCP/p97 promotes 53BP1 recruitment by removing L3MBTL1 from DNA double-strand breaks.
  Nat Struct Mol Biol, 18, 1345-1350.  
21464980 M.Ozboyaci, A.Gursoy, B.Erman, and O.Keskin (2011).
Molecular recognition of H3/H4 histone tails by the tudor domains of JMJD2A: a comparative molecular dynamics simulations study.
  PLoS One, 6, e14765.  
20669242 A.Friberg, A.Oddone, T.Klymenko, J.Müller, and M.Sattler (2010).
Structure of an atypical Tudor domain in the Drosophila Polycomblike protein.
  Protein Sci, 19, 1906-1916.
PDB code: 2xk0
  21327105 A.L.Olins, G.Rhodes, D.B.Welch, M.Zwerger, and D.E.Olins (2010).
Lamin B receptor: Multi-tasking at the nuclear envelope.
  Nucleus, 1, 53-70.  
19897549 A.M.Quinn, M.T.Bedford, A.Espejo, A.Spannhoff, C.P.Austin, U.Oppermann, and A.Simeonov (2010).
A homogeneous method for investigation of methylation-dependent protein-protein interactions in epigenetics.
  Nucleic Acids Res, 38, e11.  
20023638 J.R.Horton, A.K.Upadhyay, H.H.Qi, X.Zhang, Y.Shi, and X.Cheng (2010).
Enzymatic and structural insights for substrate specificity of a family of jumonji histone lysine demethylases.
  Nat Struct Mol Biol, 17, 38-43.
PDB codes: 3kv4 3kv5 3kv6 3kv9 3kva 3kvb
20923397 K.L.Yap, and M.M.Zhou (2010).
Keeping it in the family: diverse histone recognition by conserved structural folds.
  Crit Rev Biochem Mol Biol, 45, 488-505.  
20735237 L.Balakrishnan, and B.Milavetz (2010).
Decoding the histone H4 lysine 20 methylation mark.
  Crit Rev Biochem Mol Biol, 45, 440-452.  
20523899 L.Braun, D.Cannella, P.Ortet, M.Barakat, C.F.Sautel, S.Kieffer, J.Garin, O.Bastien, O.Voinnet, and M.A.Hakimi (2010).
A complex small RNA repertoire is generated by a plant/fungal-like machinery and effected by a metazoan-like Argonaute in the single-cell human parasite Toxoplasma gondii.
  PLoS Pathog, 6, e1000920.  
  20574068 M.D.Taylor, S.Sadhukhan, P.Kottangada, A.Ramgopal, K.Sarkar, S.D'Silva, A.Selvakumar, F.Candotti, and Y.M.Vyas (2010).
Nuclear role of WASp in the pathogenesis of dysregulated TH1 immunity in human Wiskott-Aldrich syndrome.
  Sci Transl Med, 2, 37ra44.  
20210752 M.L.Bellows, and C.A.Floudas (2010).
Computational methods for de novo protein design and its applications to the human immunodeficiency virus 1, purine nucleoside phosphorylase, ubiquitin specific protease 7, and histone demethylases.
  Curr Drug Targets, 11, 264-278.  
21095589 S.A.Miller, S.E.Mohn, and A.S.Weinmann (2010).
Jmjd3 and UTX play a demethylase-independent role in chromatin remodeling to regulate T-box family member-dependent gene expression.
  Mol Cell, 40, 594-605.  
21124763 S.Pu, A.L.Turinsky, J.Vlasblom, T.On, X.Xiong, A.Emili, Z.Zhang, J.Greenblatt, J.Parkinson, and S.J.Wodak (2010).
Expanding the landscape of chromatin modification (CM)-related functional domains and genes in human.
  PLoS One, 5, e14122.  
20210320 X.Cheng, and R.M.Blumenthal (2010).
Coordinated chromatin control: structural and functional linkage of DNA and histone methylation.
  Biochemistry, 49, 2999-3008.  
19541851 A.N.Scharf, T.K.Barth, and A.Imhof (2009).
Establishment of histone modifications after chromatin assembly.
  Nucleic Acids Res, 37, 5032-5040.  
19173732 D.Zheng, K.Zhao, and M.F.Mehler (2009).
Profiling RE1/REST-mediated histone modifications in the human genome.
  Genome Biol, 10, R9.  
19334741 G.Cui, M.V.Botuyan, and G.Mer (2009).
Preparation of recombinant peptides with site- and degree-specific lysine (13)C-methylation.
  Biochemistry, 48, 3798-3800.  
19234526 M.A.Adams-Cioaba, and J.Min (2009).
Structure and function of histone methylation binding proteins.
  Biochem Cell Biol, 87, 93.  
18923809 S.S.Ng, W.W.Yue, U.Oppermann, and R.J.Klose (2009).
Dynamic protein methylation in chromatin biology.
  Cell Mol Life Sci, 66, 407-422.  
19706462 T.M.Spektor, and J.C.Rice (2009).
Identification and characterization of posttranslational modification-specific binding proteins in vivo by mammalian tethered catalysis.
  Proc Natl Acad Sci U S A, 106, 14808-14813.  
19233876 Y.Guo, N.Nady, C.Qi, A.Allali-Hassani, H.Zhu, P.Pan, M.A.Adams-Cioaba, M.F.Amaya, A.Dong, M.Vedadi, M.Schapira, R.J.Read, C.H.Arrowsmith, and J.Min (2009).
Methylation-state-specific recognition of histones by the MBT repeat protein L3MBTL2.
  Nucleic Acids Res, 37, 2204-2210.
PDB codes: 3cey 3f70
18818090 C.Xu, G.Cui, M.V.Botuyan, and G.Mer (2008).
Structural basis for the recognition of methylated histone H3K36 by the Eaf3 subunit of histone deacetylase complex Rpd3S.
  Structure, 16, 1740-1750.
PDB codes: 2k3x 2k3y
18682226 H.van Ingen, F.M.van Schaik, H.Wienk, J.Ballering, H.Rehmann, A.C.Dechesne, J.A.Kruijzer, R.M.Liskamp, H.T.Timmers, and R.Boelens (2008).
Structural insight into the recognition of the H3K4me3 mark by the TFIID subunit TAF3.
  Structure, 16, 1245-1256.  
18451103 P.A.Cloos, J.Christensen, K.Agger, and K.Helin (2008).
Erasing the methyl mark: histone demethylases at the center of cellular differentiation and disease.
  Genes Dev, 22, 1115-1140.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.