Target Binding Site Detail
| Target General Information | Top | ||||
|---|---|---|---|---|---|
| Target ID | T18904 | Target Info | |||
| Target Name | Lysine-specific demethylase 4A (KDM4A) | ||||
| Synonyms | KIAA0677; Jumonji domain-containing protein 2A; JmjC domain-containing histone demethylation protein 3A; JMJD2A; JMJD2; JHDM3A | ||||
| Target Type | Patented-recorded Target | ||||
| Gene Name | KDM4A | ||||
| Biochemical Class | Paired donor oxygen oxidoreductase | ||||
| UniProt ID | |||||
| Ligand General Information | Top | ||||
|---|---|---|---|---|---|
| Ligand Name | N-Trimethyllysine | Ligand Info | |||
| Canonical SMILES | C[N+](C)(C)CCCCC(C(=O)O)N | ||||
| InChI | 1S/C9H20N2O2/c1-11(2,3)7-5-4-6-8(10)9(12)13/h8H,4-7,10H2,1-3H3/p+1/t8-/m0/s1 | ||||
| InChIKey | MXNRLFUSFKVQSK-QMMMGPOBSA-O | ||||
| PubChem Compound ID | 440121 | ||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| PDB ID: 4V2W JMJD2A COMPLEXED WITH NI(II), NOG AND HISTONE H3K27me3 PEPTIDE (16-35) | ||||||
| Method | X-ray diffraction | Resolution | 1.81 Å | Mutation | No | [1] |
| PDB Sequence |
TLNPSARIMT
16 FYPTMEEFRN26 FSRYIAYIES36 QGAHRAGLAK46 VVPPKEWKPR56 ASYDDIDDLV 66 IPAPIQQLVT76 GQSGLFTQYN86 IQKKAMTVRE96 FRKIANSDKY106 CTPRYSEFEE 116 LERKYWKNLT126 FNPPIYGADV136 NGTLYEKHVD146 EWNIGRLRTI156 LDLVEKESGI 166 TIEGVNTPYL176 YFGMWKTSFA186 WHTEDMDLYS196 INYLHFGEPK206 SWYSVPPEHG 216 KRLERLAKGF226 FPGSAQSCEA236 FLRHKMTLIS246 PLMLKKYGIP256 FDKVTQEAGE 266 FMITFPYGYH276 AGFNHGFNCA286 ESTNFATRRW296 IEYGKQAVLC306 SCRKDMVKIS 316 MDVFVRKFQP326 ERYKLWKAGK336 DNTVIDHTLP346 TPEAAEFL
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| PDB ID: 6H8P JMJD2A/ KDM4A COMPLEXED WITH NI(II), NOG AND Histone H1.4(18-32)K26me3 peptide (15-mer) | ||||||
| Method | X-ray diffraction | Resolution | 1.98 Å | Mutation | No | [2] |
| PDB Sequence |
NPSARIMTFY
18 PTMEEFRNFS28 RYIAYIESQG38 AHRAGLAKVV48 PPKEWKPRAS58 YDDIDDLVIP 68 APIQQLVTGQ78 SGLFTQYNIQ88 KKAMTVREFR98 KIANSDKYCT108 PRYSEFEELE 118 RKYWKNLTFN128 PPIYGADVNG138 TLYEKHVDEW148 NIGRLRTILD158 LVEKESGITI 168 EGVNTPYLYF178 GMWKTSFAWH188 TEDMDLYSIN198 YLHFGEPKSW208 YSVPPEHGKR 218 LERLAKGFFP228 GSAQSCEAFL238 RHKMTLISPL248 MLKKYGIPFD258 KVTQEAGEFM 268 ITFPYGYHAG278 FNHGFNCAES288 TNFATRRWIE298 YGKQAVLCSC308 RKDMVKISMD 318 VFVRKFQPER328 YKLWKAGKDN338 TVIDHTLPTP348 EAAEFL
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| PDB ID: 2OQ6 Crystal structure of JMJD2A complexed with histone H3 peptide trimethylated at Lys9 | ||||||
| Method | X-ray diffraction | Resolution | 2.00 Å | Mutation | No | [3] |
| PDB Sequence |
LNPSARIMTF
17 YPTMEEFRNF27 SRYIAYIESQ37 GAHRAGLAKV47 VPPKEWKPRA57 SYDDIDDLVI 67 PAPIQQLVTG77 QSGLFTQYNI87 QKKAMTVREF97 RKIANSDKYC107 TPRYSEFEEL 117 ERKYWKNLTF127 NPPIYGADVN137 GTLYEKHVDE147 WNIGRLRTIL157 DLVEKESGIT 167 IEGVNTPYLY177 FGMWKTSFAW187 HTEDMDLYSI197 NYLHFGEPKS207 WYSVPPEHGK 217 RLERLAKGFF227 PGSAQSCEAF237 LRHKMTLISP247 LMLKKYGIPF257 DKVTQEAGEF 267 MITFPYGYHA277 GFNHGFNCAE287 STNFATRRWI297 EYGKQAVLCS307 CRKDMVKISM 317 DVFVRKFQPE327 RYKLWKAGKD337 NTVIDHTLPT347 PEAAEFLK
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| PDB ID: 4V2V JMJD2A COMPLEXED WITH NI(II), NOG AND HISTONE H3K27me3 PEPTIDE (25-29) ARK(me3)SA | ||||||
| Method | X-ray diffraction | Resolution | 2.00 Å | Mutation | No | [1] |
| PDB Sequence |
SESETLNPSA
12 RIMTFYPTME22 EFRNFSRYIA32 YIESQGAHRA42 GLAKVVPPKE52 WKPRASYDDI 62 DDLVIPAPIQ72 QLVTGQSGLF82 TQYNIQKKAM92 TVREFRKIAN102 SDKYCTPRYS 112 EFEELERKYW122 KNLTFNPPIY132 GADVNGTLYE142 KHVDEWNIGR152 LRTILDLVEK 162 ESGITIEGVN172 TPYLYFGMWK182 TSFAWHTEDM192 DLYSINYLHF202 GEPKSWYSVP 212 PEHGKRLERL222 AKGFFPGSAQ232 SCEAFLRHKM242 TLISPLMLKK252 YGIPFDKVTQ 262 EAGEFMITFP272 YGYHAGFNHG282 FNCAESTNFA292 TRRWIEYGKQ302 AVLCSCRKDM 312 VKISMDVFVR322 KFQPERYKLW332 KAGKDNTVID342 HTLPTPEAAE352 FLK |
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Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .M3L or .M3L2 or .M3L3 or :3M3L;style chemicals stick;color identity;select .A:135 or .A:168 or .A:169 or .A:170 or .A:171 or .A:175 or .A:177 or .A:190 or .A:191 or .A:196 or .A:241 or .A:288 or .A:289 or .A:290 or .A:313; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| PDB ID: 2YBP JMJD2A COMPLEXED WITH R-2-HYDROXYGLUTARATE AND HISTONE H3K36me3 PEPTIDE (30-41) | ||||||
| Method | X-ray diffraction | Resolution | 2.02 Å | Mutation | No | [4] |
| PDB Sequence |
TLNPSARIMT
16 FYPTMEEFRN26 FSRYIAYIES36 QGAHRAGLAK46 VVPPKEWKPR56 ASYDDIDDLV 66 IPAPIQQLVT76 GQSGLFTQYN86 IQKKAMTVRE96 FRKIANSDKY106 CTPRYSEFEE 116 LERKYWKNLT126 FNPPIYGADV136 NGTLYEKHVD146 EWNIGRLRTI156 LDLVEKESGI 166 TIEGVNTPYL176 YFGMWKTSFA186 WHTEDMDLYS196 INYLHFGEPK206 SWYSVPPEHG 216 KRLERLAKGF226 FPGSAQSCEA236 FLRHKMTLIS246 PLMLKKYGIP256 FDKVTQEAGE 266 FMITFPYGYH276 AGFNHGFNCA286 ESTNFATRRW296 IEYGKQAVLC306 SCRKDMVKIS 316 MDVFVRKFQP326 ERYKLWKAGK336 DNTVIDHTLP346 TPEAAEFLK
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Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .M3L or .M3L2 or .M3L3 or :3M3L;style chemicals stick;color identity;select .A:135 or .A:168 or .A:169 or .A:170 or .A:171 or .A:175 or .A:177 or .A:190 or .A:191 or .A:196 or .A:241 or .A:288 or .A:289 or .A:290 or .A:313; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| PDB ID: 3U4S Histone Lysine demethylase JMJD2A in complex with T11C peptide substrate crosslinked to N-oxalyl-D-cysteine | ||||||
| Method | X-ray diffraction | Resolution | 2.15 Å | Mutation | Yes | [5] |
| PDB Sequence |
LNPSARIMTF
17 YPTMEEFRNF27 SRYIAYIESQ37 GAHRAGLAKV47 VPPKEWKPRA57 SYDDIDDLVI 67 PAPIQQLVTG77 QSGLFTQYNI87 QKKAMTVREF97 RKIANSDKYC107 TPRYSEFEEL 117 ERKYWKNLTF127 NPPIYGADVN137 GTLYEKHVDE147 WNIGRLRTIL157 DLVEKESGIT 167 IEGVNTPYLY177 FGMWKTSFAW187 HTEDMDLYSI197 NYLHFGEPKS207 WYSVPPEHGK 217 RLERLAKGFF227 PGSAQSCEAF237 LRHKMTLISP247 LMLKKYGIPF257 DKVTQEAGEF 267 MITFPYGYHA277 GFNHGFNCAE287 STNFATRRWI297 EYGKQAVLCS307 CRKDMVKISM 317 DVFVRKFQPE327 RYKLWKAGKD337 NTVIDHTLPT347 PEAAE
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Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .M3L or .M3L2 or .M3L3 or :3M3L;style chemicals stick;color identity;select .A:135 or .A:168 or .A:169 or .A:170 or .A:171 or .A:173 or .A:175 or .A:177 or .A:190 or .A:191 or .A:196 or .A:197 or .A:198 or .A:241 or .A:288 or .A:289 or .A:290 or .A:313; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| PDB ID: 2OS2 Crystal structure of JMJD2A complexed with histone H3 peptide trimethylated at Lys36 | ||||||
| Method | X-ray diffraction | Resolution | 2.30 Å | Mutation | No | [3] |
| PDB Sequence |
LNPSARIMTF
17 YPTMEEFRNF27 SRYIAYIESQ37 GAHRAGLAKV47 VPPKEWKPRA57 SYDDIDDLVI 67 PAPIQQLVTG77 QSGLFTQYNI87 QKKAMTVREF97 RKIANSDKYC107 TPRYSEFEEL 117 ERKYWKNLTF127 NPPIYGADVN137 GTLYEKHVDE147 WNIGRLRTIL157 DLVEKESGIT 167 IEGVNTPYLY177 FGMWKTSFAW187 HTEDMDLYSI197 NYLHFGEPKS207 WYSVPPEHGK 217 RLERLAKGFF227 PGSAQSCEAF237 LRHKMTLISP247 LMLKKYGIPF257 DKVTQEAGEF 267 MITFPYGYHA277 GFNHGFNCAE287 STNFATRRWI297 EYGKQAVLCS307 CRKDMVKISM 317 DVFVRKFQPE327 RYKLWKAGKD337 NTVIDHTLPT347 PEAAEFL
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Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .M3L or .M3L2 or .M3L3 or :3M3L;style chemicals stick;color identity;select .A:135 or .A:168 or .A:169 or .A:170 or .A:171 or .A:175 or .A:177 or .A:190 or .A:191 or .A:196 or .A:241 or .A:288 or .A:289 or .A:290 or .A:313; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| PDB ID: 2YBS JMJD2A COMPLEXED WITH S-2-HYDROXYGLUTARATE AND HISTONE H3K36me3 PEPTIDE (30-41) | ||||||
| Method | X-ray diffraction | Resolution | 2.32 Å | Mutation | No | [4] |
| PDB Sequence |
LNPSARIMTF
17 YPTMEEFRNF27 SRYIAYIESQ37 GAHRAGLAKV47 VPPKEWKPRA57 SYDDIDDLVI 67 PAPIQQLVTG77 QSGLFTQYNI87 QKKAMTVREF97 RKIANSDKYC107 TPRYSEFEEL 117 ERKYWKNLTF127 NPPIYGADVN137 GTLYEKHVDE147 WNIGRLRTIL157 DLVEKESGIT 167 IEGVNTPYLY177 FGMWKTSFAW187 HTEDMDLYSI197 NYLHFGEPKS207 WYSVPPEHGK 217 RLERLAKGFF227 PGSAQSCEAF237 LRHKMTLISP247 LMLKKYGIPF257 DKVTQEAGEF 267 MITFPYGYHA277 GFNHGFNCAE287 STNFATRRWI297 EYGKQAVLCS307 CRKDMVKISM 317 DVFVRKFQPE327 RYKLWKAGKD337 NTVIDHTLPT347 PEAAEFLK
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Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .M3L or .M3L2 or .M3L3 or :3M3L;style chemicals stick;color identity;select .A:135 or .A:168 or .A:169 or .A:170 or .A:171 or .A:175 or .A:177 or .A:190 or .A:191 or .A:196 or .A:241 or .A:288 or .A:289 or .A:290 or .A:313; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| PDB ID: 5LY2 JMJD2A/ KDM4A COMPLEXED WITH NI(II), NOG AND Macrocyclic PEPTIDE Inhibitor CP2_R6Kme3 (13-mer) | ||||||
| Method | X-ray diffraction | Resolution | 2.43 Å | Mutation | No | [6] |
| PDB Sequence |
TLNPSARIMT
16 FYPTMEEFRN26 FSRYIAYIES36 QGAHRAGLAK46 VVPPKEWKPR56 ASYDDIDDLV 66 IPAPIQQLVT76 GQSGLFTQYN86 IQKKAMTVRE96 FRKIANSDKY106 CTPRYSEFEE 116 LERKYWKNLT126 FNPPIYGADV136 NGTLYEKHVD146 EWNIGRLRTI156 LDLVEKESGI 166 TIEGVNTPYL176 YFGMWKTSFA186 WHTEDMDLYS196 INYLHFGEPK206 SWYSVPPEHG 216 KRLERLAKGF226 FPGSAQSCEA236 FLRHKMTLIS246 PLMLKKYGIP256 FDKVTQEAGE 266 FMITFPYGYH276 AGFNHGFNCA286 ESTNFATRRW296 IEYGKQAVLC306 SCRKDMVKIS 316 MDVFVRKFQP326 ERYKLWKAGK336 DNTVIDHTLP346 TPEAAEFL
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Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .M3L or .M3L2 or .M3L3 or :3M3L;style chemicals stick;color identity;select .A:135 or .A:169 or .A:170 or .A:171 or .A:175 or .A:177 or .A:190 or .A:191 or .A:196 or .A:241 or .A:288 or .A:289 or .A:290; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| PDB ID: 2P5B The complex structure of JMJD2A and trimethylated H3K36 peptide | ||||||
| Method | X-ray diffraction | Resolution | 1.99 Å | Mutation | Yes | [7] |
| PDB Sequence |
ASESETLNPS
11 ARIMTFYPTM21 EEFRNFSRYI31 AYIESQGAHR41 AGLAKVVPPK51 EWKPRASYDD 61 IDDLVIPAPI71 QQLVTGQSGL81 FTQYNIQKKA91 MTVREFRKIA101 NSDKYCTPRY 111 SEFEELERKY121 WKNLTFNPPI131 YGADVNGTLY141 EKHVDEWNIG151 RLRTILDLVE 161 KESGITIEGV171 NTPYLYFGMW181 KTSFAWHTED191 MDLYSINYLH201 FGEPKSWYSV 211 PPEHGKRLER221 LAKGFFPGSA231 QSCEAFLRHK241 MTLISPLMLK251 KYGIPFDKVT 261 QEAGEFMITF271 PYGYHAGFNH281 GFNCAESTNF291 ATRRWIEYGK301 QAVLCSCRKD 311 MVKISMDVFV321 RKFQPERYKL331 WKAGKDNTVI341 DHTLPTP
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Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .M3L or .M3L2 or .M3L3 or :3M3L;style chemicals stick;color identity;select .A:135 or .A:168 or .A:169 or .A:170 or .A:171 or .A:175 or .A:177 or .A:190 or .A:191 or .A:196 or .A:241 or .A:288 or .A:289 or .A:290 or .A:313; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| PDB ID: 2Q8C Crystal structure of JMJD2A in ternary complex with an histone H3K9me3 peptide and 2-oxoglutarate | ||||||
| Method | X-ray diffraction | Resolution | 2.05 Å | Mutation | No | [8] |
| PDB Sequence |
SESETLNPSA
12 RIMTFYPTME22 EFRNFSRYIA32 YIESQGAHRA42 GLAKVVPPKE52 WKPRASYDDI 62 DDLVIPAPIQ72 QLVTGQSGLF82 TQYNIQKKAM92 TVREFRKIAN102 SDKYCTPRYS 112 EFEELERKYW122 KNLTFNPPIY132 GADVNGTLYE142 KHVDEWNIGR152 LRTILDLVEK 162 ESGITIEGVN172 TPYLYFGMWK182 TSFAWHTEDM192 DLYSINYLHF202 GEPKSWYSVP 212 PEHGKRLERL222 AKGFFPGSAQ232 SCEAFLRHKM242 TLISPLMLKK252 YGIPFDKVTQ 262 EAGEFMITFP272 YGYHAGFNHG282 FNCAESTNFA292 TRRWIEYGKQ302 AVLCSCRKDM 312 VKISMDVFVR322 KFQPERYKLW332 KAGKDNTVID342 HTLPT
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Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .M3L or .M3L2 or .M3L3 or :3M3L;style chemicals stick;color identity;select .A:135 or .A:168 or .A:169 or .A:170 or .A:171 or .A:175 or .A:177 or .A:190 or .A:191 or .A:196 or .A:241 or .A:288 or .A:289 or .A:290 or .A:313; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| PDB ID: 2Q8E Specificity and Mechanism of JMJD2A, a Trimethyllysine-Specific Histone Demethylase | ||||||
| Method | X-ray diffraction | Resolution | 2.05 Å | Mutation | No | [8] |
| PDB Sequence |
SESETLNPSA
12 RIMTFYPTME22 EFRNFSRYIA32 YIESQGAHRA42 GLAKVVPPKE52 WKPRASYDDI 62 DDLVIPAPIQ72 QLVTGQSGLF82 TQYNIQKKAM92 TVREFRKIAN102 SDKYCTPRYS 112 EFEELERKYW122 KNLTFNPPIY132 GADVNGTLYE142 KHVDEWNIGR152 LRTILDLVEK 162 ESGITIEGVN172 TPYLYFGMWK182 TSFAWHTEDM192 DLYSINYLHF202 GEPKSWYSVP 212 PEHGKRLERL222 AKGFFPGSAQ232 SCEAFLRHKM242 TLISPLMLKK252 YGIPFDKVTQ 262 EAGEFMITFP272 YGYHAGFNHG282 FNCAESTNFA292 TRRWIEYGKQ302 AVLCSCRKDM 312 VKISMDVFVR322 KFQPERYKLW332 KAGKDNTVID342 HTLP
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Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .M3L or .M3L2 or .M3L3 or :3M3L;style chemicals stick;color identity;select .A:135 or .A:168 or .A:169 or .A:170 or .A:171 or .A:175 or .A:177 or .A:190 or .A:191 or .A:196 or .A:241 or .A:288 or .A:289 or .A:290 or .A:313; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| References | Top | ||||
|---|---|---|---|---|---|
| REF 1 | Studies on the catalytic domains of multiple JmjC oxygenases using peptide substrates. Epigenetics. 2014 Dec;9(12):1596-603. | ||||
| REF 2 | Mechanistic and structural studies of KDM-catalysed demethylation of histone 1 isotype 4 at lysine 26. FEBS Lett. 2018 Oct;592(19):3264-3273. | ||||
| REF 3 | Crystal structures of histone demethylase JMJD2A reveal basis for substrate specificity. Nature. 2007 Jul 5;448(7149):87-91. | ||||
| REF 4 | The oncometabolite 2-hydroxyglutarate inhibits histone lysine demethylases. EMBO Rep. 2011 May;12(5):463-9. | ||||
| REF 5 | Linking of 2-oxoglutarate and substrate binding sites enables potent and highly selective inhibition of JmjC histone demethylases. Angew Chem Int Ed Engl. 2012 Feb 13;51(7):1631-4. | ||||
| REF 6 | Highly selective inhibition of histone demethylases by de novo macrocyclic peptides. Nat Commun. 2017 Apr 6;8:14773. | ||||
| REF 7 | Structural basis of the recognition of a methylated histone tail by JMJD2A. Proc Natl Acad Sci U S A. 2007 Jun 26;104(26):10818-23. | ||||
| REF 8 | Specificity and mechanism of JMJD2A, a trimethyllysine-specific histone demethylase. Nat Struct Mol Biol. 2007 Aug;14(8):689-95. | ||||
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