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(-) Description

Title :  CRYSTAL STRUCTURE OF THE CXXC AND PHD DOMAIN OF HUMAN LYSINE-SPECIFIC DEMETHYLASE 2A (KDM2A)(FBXL11)
 
Authors :  C. K. Allerston, A. A. Watson, C. Edlich, B. Li, Y. Chen, L. Ball, T. Kroje C. H. Arrowsmith, A. Edwards, C. Bountra, F. Von Delft, E. D. Laue, O. G
Date :  27 Sep 12  (Deposition) - 10 Oct 12  (Release) - 10 Oct 12  (Revision)
Method :  X-RAY DIFFRACTION
Resolution :  2.24
Chains :  Asym. Unit :  A,B
Biol. Unit 1:  A  (1x)
Biol. Unit 2:  B  (1x)
Keywords :  Oxidoreductase, Ubiquitin, Ligase, Ubiquitination, Demethylation, Zf-Cxxc Dna Binding Domain, Cpg Island, Chromatin, Kdm2A, Fbxl11 (Keyword Search: [Gene Ontology, PubMed, Web (Google))
 
Reference :  C. K. Allerston, A. A. Watson, C. Edlich, B. Li, Y. Chen, L. Ball, T. Krojer, C. H. Arrowsmith, A. Edwards, C. Bountra, F. Von Delft, E. D. Laue, O. Gileadi
Crystal Structure Of The Cxxc And Phd Domain Of Human Lysine-Specific Demethylase 2A (Kdm2A)( Fbxl11)
To Be Published
PubMed: search

(-) Compounds

Molecule 1 - LYSINE-SPECIFIC DEMETHYLASE 2A
    ChainsA, B
    EC Number1.14.11.27
    EngineeredYES
    Expression SystemESCHERICHIA COLI
    Expression System PlasmidPNIC28-BSA4
    Expression System StrainBL21(DE3)
    Expression System Taxid469008
    Expression System VariantR3-PRARE2
    Expression System Vector TypePLASMID
    FragmentCXXC AND PHD DOMAIN, RESIDUES 567-681
    Organism CommonHUMAN
    Organism ScientificHOMO SAPIENS
    Organism Taxid9606
    SynonymCXXC-TYPE ZINC FINGER PROTEIN 8, F-BOX AND LEUCINE-RICH REPEAT PROTEIN 11, F-BOX PROTEIN FBL7, F-BOX PROTEIN LILINA, F-BOX/LRR-REPEAT PROTEIN 11, JMJC DOMAIN-CONTAINING HISTONE DEMETHYLATION PROTEIN 1A, [HISTONE-H3]-LYSINE-36 DEMETHYLASE 1A

 Structural Features

(-) Chains, Units

  12
Asymmetric Unit AB
Biological Unit 1 (1x)A 
Biological Unit 2 (1x) B

Summary Information (see also Sequences/Alignments below)

(-) Ligands, Modified Residues, Ions  (2, 9)

Asymmetric Unit (2, 9)
No.NameCountTypeFull Name
1EDO1Ligand/Ion1,2-ETHANEDIOL
2ZN8Ligand/IonZINC ION
Biological Unit 1 (1, 1)
No.NameCountTypeFull Name
1EDO1Ligand/Ion1,2-ETHANEDIOL
2ZN-1Ligand/IonZINC ION
Biological Unit 2 (0, 0)
No.NameCountTypeFull Name
1EDO-1Ligand/Ion1,2-ETHANEDIOL
2ZN-1Ligand/IonZINC ION

(-) Sites  (9, 9)

Asymmetric Unit (9, 9)
No.NameEvidenceResiduesDescription
1AC1SOFTWAREASP A:657 , GLY A:658 , HOH A:2049 , LYS B:601 , GLN B:602 , HOH B:2006 , HOH B:2029BINDING SITE FOR RESIDUE EDO A1677
2AC2SOFTWARECYS B:582 , CYS B:585 , CYS B:588 , CYS B:604BINDING SITE FOR RESIDUE ZN B1677
3AC3SOFTWARECYS A:582 , CYS A:585 , CYS A:588 , CYS A:604BINDING SITE FOR RESIDUE ZN A1678
4AC4SOFTWARECYS A:571 , CYS A:574 , CYS A:577 , CYS A:609BINDING SITE FOR RESIDUE ZN A1679
5AC5SOFTWARECYS B:571 , CYS B:574 , CYS B:577 , CYS B:609BINDING SITE FOR RESIDUE ZN B1678
6AC6SOFTWARECYS A:642 , CYS A:645 , CYS A:672 , CYS A:675BINDING SITE FOR RESIDUE ZN A1680
7AC7SOFTWARECYS A:620 , CYS A:623 , HIS A:650 , CYS A:653BINDING SITE FOR RESIDUE ZN A1681
8AC8SOFTWARECYS B:642 , CYS B:645 , CYS B:672 , CYS B:675BINDING SITE FOR RESIDUE ZN B1679
9AC9SOFTWARECYS B:620 , CYS B:623 , HIS B:650 , CYS B:653BINDING SITE FOR RESIDUE ZN B1680

(-) SS Bonds  (0, 0)

(no "SS Bond" information available for 4BBQ)

(-) Cis Peptide Bonds  (0, 0)

(no "Cis Peptide Bond" information available for 4BBQ)

 Sequence-Structure Mapping

(-) SAPs(SNPs)/Variants  (0, 0)

(no "SAP(SNP)/Variant" information available for 4BBQ)

(-) PROSITE Motifs  (2, 4)

Asymmetric Unit (2, 4)
 PROSITEUniProtKBPDB
No.IDACDescriptionIDLocationCountLocation
1ZF_PHD_2PS50016 Zinc finger PHD-type profile.KDM2A_HUMAN617-678
 
  2A:617-676
B:617-676
2ZF_PHD_1PS01359 Zinc finger PHD-type signature.KDM2A_HUMAN620-675
 
  2A:620-675
B:620-675
Biological Unit 1 (2, 2)
 PROSITEUniProtKBPDB
No.IDACDescriptionIDLocationCountLocation
1ZF_PHD_2PS50016 Zinc finger PHD-type profile.KDM2A_HUMAN617-678
 
  1A:617-676
-
2ZF_PHD_1PS01359 Zinc finger PHD-type signature.KDM2A_HUMAN620-675
 
  1A:620-675
-
Biological Unit 2 (2, 2)
 PROSITEUniProtKBPDB
No.IDACDescriptionIDLocationCountLocation
1ZF_PHD_2PS50016 Zinc finger PHD-type profile.KDM2A_HUMAN617-678
 
  1-
B:617-676
2ZF_PHD_1PS01359 Zinc finger PHD-type signature.KDM2A_HUMAN620-675
 
  1-
B:620-675

(-) Exons   (0, 0)

(no "Exon" information available for 4BBQ)

(-) Sequences/Alignments

Asymmetric Unit
   Reformat: Number of residues per line =  ('0' or empty: single-line sequence representation)
  Number of residues per labelling interval =   
  UniProt sequence: complete  aligned part    
   Show mapping: SCOP domains CATH domains Pfam domains Secondary structure (by author)
SAPs(SNPs) PROSITE motifs Exons
(details for a mapped element are shown in a popup box when the mouse pointer rests over it)
Chain A from PDB  Type:PROTEIN  Length:111
 aligned with KDM2A_HUMAN | Q9Y2K7 from UniProtKB/Swiss-Prot  Length:1162

    Alignment length:111
                                   575       585       595       605       615       625       635       645       655       665       675 
          KDM2A_HUMAN   566 RRRVRCRKCKACVQGECGVCHYCRDMKKFGGPGRMKQSCVLRQCLAPRLPHSVTCSLCGEVDQNEETQDFEKKLMECCICNEIVHPGCLQMDGEGLLNEELPNCWECPKCY 676
               SCOP domains --------------------------------------------------------------------------------------------------------------- SCOP domains
               CATH domains --------------------------------------------------------------------------------------------------------------- CATH domains
               Pfam domains --------------------------------------------------------------------------------------------------------------- Pfam domains
         Sec.struct. author ........hhhhhh.....hhhhhhhhhhh........hhhhh...................hhhhhhhhhhh.eee.....eehhhhh......ee......eee..... Sec.struct. author
                 SAPs(SNPs) --------------------------------------------------------------------------------------------------------------- SAPs(SNPs)
                PROSITE (1) ---------------------------------------------------ZF_PHD_2  PDB: A:617-676 UniProt: 617-678                    PROSITE (1)
                PROSITE (2) ------------------------------------------------------ZF_PHD_1  PDB: A:620-675 UniProt: 620-675               - PROSITE (2)
                 Transcript --------------------------------------------------------------------------------------------------------------- Transcript
                 4bbq A   0 MRRVRCRKCKACVQGECGVCHYCRDMKKFGGPGRMKQSCVLRQCLAPRLPHSVTCSLCGEVDQNEETQDFEKKLMECCICNEIVHPGCLQMDGEGLLNEELPNCWECPKCY 676
                            ||     575       585       595       605       615       625       635       645       655       665       675 
                            ||                                                                                                             
                            0|                                                                                                             
                           567                                                                                                             

Chain B from PDB  Type:PROTEIN  Length:106
 aligned with KDM2A_HUMAN | Q9Y2K7 from UniProtKB/Swiss-Prot  Length:1162

    Alignment length:111
                                   575       585       595       605       615       625       635       645       655       665       675 
          KDM2A_HUMAN   566 RRRVRCRKCKACVQGECGVCHYCRDMKKFGGPGRMKQSCVLRQCLAPRLPHSVTCSLCGEVDQNEETQDFEKKLMECCICNEIVHPGCLQMDGEGLLNEELPNCWECPKCY 676
               SCOP domains --------------------------------------------------------------------------------------------------------------- SCOP domains
               CATH domains --------------------------------------------------------------------------------------------------------------- CATH domains
               Pfam domains --------------------------------------------------------------------------------------------------------------- Pfam domains
         Sec.struct. author ........hhhhhh.....hhhhhhhhhhh........hhhhh.....................-----.....eee.....eehhhhh......ee......eee..... Sec.struct. author
                 SAPs(SNPs) --------------------------------------------------------------------------------------------------------------- SAPs(SNPs)
                PROSITE (1) ---------------------------------------------------ZF_PHD_2  PDB: B:617-676 UniProt: 617-678                    PROSITE (1)
                PROSITE (2) ------------------------------------------------------ZF_PHD_1  PDB: B:620-675 UniProt: 620-675               - PROSITE (2)
                 Transcript --------------------------------------------------------------------------------------------------------------- Transcript
                 4bbq B   0 MRRVRCRKCKACVQGECGVCHYCRDMKKFGGPGRMKQSCVLRQCLAPRLPHSVTCSLCGEVDQN-----FEKKLMECCICNEIVHPGCLQMDGEGLLNEELPNCWECPKCY 676
                            ||     575       585       595       605       615       625   |   635       645       655       665       675 
                            0|                                                           629   635                                         
                           567                                                                                                             

   Legend:   → Mismatch (orange background)
  - → Gap (green background, '-', border residues have a numbering label)
    → Modified Residue (blue background, lower-case, 'x' indicates undefined single-letter code, labelled with number + name)
  x → Chemical Group (purple background, 'x', labelled with number + name, e.g. ACE or NH2)
  extra numbering lines below/above indicate numbering irregularities and modified residue names etc., number ends below/above '|'

 Classification and Annotation

(-) SCOP Domains  (0, 0)

(no "SCOP Domain" information available for 4BBQ)

(-) CATH Domains  (0, 0)

(no "CATH Domain" information available for 4BBQ)

(-) Pfam Domains  (0, 0)

(no "Pfam Domain" information available for 4BBQ)

(-) Gene Ontology  (15, 15)

Asymmetric Unit(hide GO term definitions)
Chain A,B   (KDM2A_HUMAN | Q9Y2K7)
molecular function
    GO:0003677    DNA binding    Any molecular function by which a gene product interacts selectively and non-covalently with DNA (deoxyribonucleic acid).
    GO:0051213    dioxygenase activity    Catalysis of an oxidation-reduction (redox) reaction in which both atoms of oxygen from one molecule of O2 are incorporated into the (reduced) product(s) of the reaction. The two atoms of oxygen may be distributed between two different products.
    GO:0032452    histone demethylase activity    Catalysis of the removal of a methyl group from a histone.
    GO:0051864    histone demethylase activity (H3-K36 specific)    Catalysis of the reaction: histone H3 N6-methyl-L-lysine (position 36) + alpha-ketoglutarate + O2 = succinate + CO2 + formaldehyde + lysine. This reaction is the removal of a methyl group from lysine at position 36 of the histone H3 protein.
    GO:0046872    metal ion binding    Interacting selectively and non-covalently with any metal ion.
    GO:0016491    oxidoreductase activity    Catalysis of an oxidation-reduction (redox) reaction, a reversible chemical reaction in which the oxidation state of an atom or atoms within a molecule is altered. One substrate acts as a hydrogen or electron donor and becomes oxidized, while the other acts as hydrogen or electron acceptor and becomes reduced.
    GO:0008270    zinc ion binding    Interacting selectively and non-covalently with zinc (Zn) ions.
biological process
    GO:0006303    double-strand break repair via nonhomologous end joining    The repair of a double-strand break in DNA in which the two broken ends are rejoined with little or no sequence complementarity. Information at the DNA ends may be lost due to the modification of broken DNA ends. This term covers instances of separate pathways, called classical (or canonical) and alternative nonhomologous end joining (C-NHEJ and A-NHEJ). These in turn may further branch into sub-pathways, but evidence is still unclear.
    GO:0070544    histone H3-K36 demethylation    The modification of histone H3 by the removal of a methyl group from lysine at position 36 of the histone.
    GO:0055114    oxidation-reduction process    A metabolic process that results in the removal or addition of one or more electrons to or from a substance, with or without the concomitant removal or addition of a proton or protons.
    GO:0006355    regulation of transcription, DNA-templated    Any process that modulates the frequency, rate or extent of cellular DNA-templated transcription.
    GO:0006351    transcription, DNA-templated    The cellular synthesis of RNA on a template of DNA.
cellular component
    GO:0005730    nucleolus    A small, dense body one or more of which are present in the nucleus of eukaryotic cells. It is rich in RNA and protein, is not bounded by a limiting membrane, and is not seen during mitosis. Its prime function is the transcription of the nucleolar DNA into 45S ribosomal-precursor RNA, the processing of this RNA into 5.8S, 18S, and 28S components of ribosomal RNA, and the association of these components with 5S RNA and proteins synthesized outside the nucleolus. This association results in the formation of ribonucleoprotein precursors; these pass into the cytoplasm and mature into the 40S and 60S subunits of the ribosome.
    GO:0005654    nucleoplasm    That part of the nuclear content other than the chromosomes or the nucleolus.
    GO:0005634    nucleus    A membrane-bounded organelle of eukaryotic cells in which chromosomes are housed and replicated. In most cells, the nucleus contains all of the cell's chromosomes except the organellar chromosomes, and is the site of RNA synthesis and processing. In some species, or in specialized cell types, RNA metabolism or DNA replication may be absent.

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        KDM2A_HUMAN | Q9Y2K72yu1 2yu2

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