Target Binding Site Detail
| Target General Information | Top | ||||
|---|---|---|---|---|---|
| Target ID | T69563 | Target Info | |||
| Target Name | Oxalosuccinate decarboxylase (IDH1) | ||||
| Synonyms | PICD; NADP(+)-specific ICDH; Isocitrate dehydrogenase [NADP] cytoplasmic; IDP; IDH; Cytosolic NADP-isocitrate dehydrogenase | ||||
| Target Type | Successful Target | ||||
| Gene Name | IDH1 | ||||
| Biochemical Class | Short-chain dehydrogenases reductase | ||||
| UniProt ID | |||||
| Ligand General Information | Top | ||||
|---|---|---|---|---|---|
| Ligand Name | Isocitric Acid | Ligand Info | |||
| Canonical SMILES | C(C(C(C(=O)O)O)C(=O)O)C(=O)O | ||||
| InChI | 1S/C6H8O7/c7-3(8)1-2(5(10)11)4(9)6(12)13/h2,4,9H,1H2,(H,7,8)(H,10,11)(H,12,13) | ||||
| InChIKey | ODBLHEXUDAPZAU-UHFFFAOYSA-N | ||||
| PubChem Compound ID | 1198 | ||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| PDB ID: 6PAY Structure of HsICDH1:Mg(II):ICT:NADPH(50%) complex reveals structural basis for observation of half-sites reactivity | ||||||
| Method | X-ray diffraction | Resolution | 2.20 Å | Mutation | No | [1] |
| PDB Sequence |
KISGGSVVEM
13 QGDEMTRIIW23 ELIKEKLIFP33 YVELDLHSYD43 LGIENRDATN53 DQVTKDAAEA 63 IKKHNVGVKC73 ATITPDEKRV83 EEFKLKQMWK93 SPNGTIRNIL103 GGTVFREAII 113 CKNIPRLVSG123 WVKPIIIGRH133 AYGDQYRATD143 FVVPGPGKVE153 ITYTPSDGTQ 163 KVTYLVHNFE173 EGGGVAMGMY183 NQDKSIEDFA193 HSSFQMALSK203 GWPLYLSTKN 213 TILKKYDGRF223 KDIFQEIYDK233 QYKSQFEAQK243 IWYEHRLIDD253 MVAQAMKSEG 263 GFIWACKNYD273 GDVQSDSVAQ283 GYGSLGMMTS293 VLVCPDGKTV303 EAEAAHGTVT 313 RHYRMYQKGQ323 ETSTNPIASI333 FAWTRGLAHR343 AKLDNNKELA353 FFANALEEVS 363 IETIEAGFMT373 KDLAACIKGL383 PNVQRSDYLN393 TFEFMDKLGE403 NLKIKLAQA |
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| PDB ID: 1T0L Crystal structure of human cytosolic NADP(+)-dependent isocitrate dehydrogenase in complex with NADP, isocitrate, and calcium(2+) | ||||||
| Method | X-ray diffraction | Resolution | 2.41 Å | Mutation | No | [2] |
| PDB Sequence |
MSKKISGGSV
10 VEMQGDEMTR20 IIWELIKEKL30 IFPYVELDLH40 SYDLGIENRD50 ATNDQVTKDA 60 AEAIKKHNVG70 VKCATITPDE80 KRVEEFKLKQ90 MWKSPNGTIR100 NILGGTVFRE 110 AIICKNIPRL120 VSGWVKPIII130 GRHAYGDQYR140 ATDFVVPGPG150 KVEITYTPSD 160 GTQKVTYLVH170 NFEEGGGVAM180 GMYNQDKSIE190 DFAHSSFQMA200 LSKGWPLYLS 210 TKNTILKKYD220 GRFKDIFQEI230 YDKQYKSQFE240 AQKIWYEHRL250 IDDMVAQAMK 260 SEGGFIWACK270 NYDGDVQSDS280 VAQGYGSLGM290 MTSVLVCPDG300 KTVEAEAAHG 310 TVTRHYRMYQ320 KGQETSTNPI330 ASIFAWTRGL340 AHRAKLDNNK350 ELAFFANALE 360 EVSIETIEAG370 FMTKDLAACI380 KGLPNVQRSD390 YLNTFEFMDK400 LGENLKIKLA 410 QAKL
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| PDB ID: 5YFN Human isocitrate dehydrogenase 1 bound with isocitrate | ||||||
| Method | X-ray diffraction | Resolution | 2.50 Å | Mutation | No | [3] |
| PDB Sequence |
NLYFQSMMSK
3 KISGGSVVEM13 QGDEMTRIIW23 ELIKEKLIFP33 YVELDLHSYD43 LGIENRDATN 53 DQVTKDAAEA63 IKKHNVGVKC73 ATITPDEKRV83 EEFKLKQMWK93 SPNGTIRNIL 103 GGTVFREAII113 CKNIPRLVSG123 WVKPIIIGRH133 AYGDQYRATD143 FVVPGPGKVE 153 ITYTPSDGTQ163 KVTYLVHNFE173 EGGGVAMGMY183 NQDKSIEDFA193 HSSFQMALSK 203 GWPLYLSTKN213 TILKKYDGRF223 KDIFQEIYDK233 QYKSQFEAQK243 IWYEHRLIDD 253 MVAQAMKSEG263 GFIWACKNYD273 GDVQSDSVAQ283 GYGSLGMMTS293 VLVCPDGKTV 303 EAEAAHGTVT313 RHYRMYQKGQ323 ETSTNPIASI333 FAWTRGLAHR343 AKLDNNKELA 353 FFANALEEVS363 IETIEAGFMT373 KDLAACIKGL383 PNVQRSDYLN393 TFEFMDKLGE 403 NLKIKLAQ
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| PDB ID: 3MAP Crystal structure of homodimeric R132H mutant of human cytosolic NADP(+)-dependent isocitrate dehydrogenase in complex with NADP and isocitrate | ||||||
| Method | X-ray diffraction | Resolution | 2.80 Å | Mutation | Yes | [4] |
| PDB Sequence |
KKISGGSVVE
12 MQGDEMTRII22 WELIKEKLIF32 PYVELDLHSY42 DLGIENRDAT52 NDQVTKDAAE 62 AIKKHNVGVK72 CATITPDEKR82 VEEFKLKQMW92 KSPNGTIRNI102 LGGTVFREAI 112 ICKNIPRLVS122 GWVKPIIIGH132 HARATDFVVP147 GPGKVEITYT157 PSDGTQKVTY 167 LVHNFEEGGG177 VAMGMYNQDK187 SIEDFAHSSF197 QMALSKGWPL207 YLSTKNTILK 217 KYDGRFKDIF227 QEIYDKQYKS237 QFEAQKIWYE247 HRLIDDMVAQ257 AMKSEGGFIW 267 ACKNVAQGYG286 SLGMMTSVLV296 CPDGKTVEAE306 AAHGTVTRHY316 RMYQKGQETS 326 TNPIASIFAW336 TRGLAHRAKL346 DNNKELAFFA356 NALEEVSIET366 IEAGFMTKDL 376 AACIKGLPNV386 QRSDYLNTFE396 FMDKLGENLK406 IKLAQAK
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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 .ICT or .ICT2 or .ICT3 or :3ICT;style chemicals stick;color identity;select .A:75 or .A:77 or .A:94 or .A:96 or .A:97 or .A:100 or .A:109 or .A:308; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| PDB ID: 3MAS Crystal structure of heterodimeric R132H mutant of human cytosolic NADP(+)-dependent isocitrate dehydrogenase in complex with NADP and isocitrate | ||||||
| Method | X-ray diffraction | Resolution | 3.20 Å | Mutation | Yes | [4] |
| PDB Sequence |
> Chain A
KKISGGSVVE 12 MQGDEMTRII22 WELIKEKLIF32 PYVELDLHSY42 DLGIENRDAT52 NDQVTKDAAE 62 AIKKHNVGVK72 CATITPDEKR82 VEEFKLKQMW92 KSPNGTIRNI102 LGGTVFREAI 112 ICKNIPRLVS122 GWVKPIIIGH132 HARATDFVVP147 GPGKVEITYT157 PSDGTQKVTY 167 LVHNFEEGGG177 VAMGMYNQDK187 SIEDFAHSSF197 QMALSKGWPL207 YLSTKNTILK 217 KYDGRFKDIF227 QEIYDKQYKS237 QFEAQKIWYE247 HRLIDDMVAQ257 AMKSEGGFIW 267 ACKNGSLGMM291 TSVLVCPDGK301 TVEAEAAHGT311 VTRHYRMYQK321 GQETSTNPIA 331 SIFAWTRGLA341 HRAKLDNNKE351 LAFFANALEE361 VSIETIEAGF371 MTKDLAACIK 381 GLPNVQRSDY391 LNTFEFMDKL401 GENLKIKLAQ411 AKL> Chain B KKISGGSVVE 12 MQGDEMTRII22 WELIKEKLIF32 PYVELDLHSY42 DLGIENRDAT52 NDQVTKDAAE 62 AIKKHNVGVK72 CATITPDEKR82 VEEFKLKQMW92 KSPNGTIRNI102 LGGTVFREAI 112 ICKNIPRLVS122 GWVKPIIIGR132 HARATDFVVP147 GPGKVEITYT157 PSDGTQKVTY 167 LVHNFEEGGG177 VAMGMYNQDK187 SIEDFAHSSF197 QMALSKGWPL207 YLSTKNTILK 217 KYDGRFKDIF227 QEIYDKQYKS237 QFEAQKIWYE247 HRLIDDMVAQ257 AMKSEGGFIW 267 ACKNYGSLGM290 MTSVLVCPDG300 KTVEAEAAHG310 TVTRHYRMYQ320 KGQETSTNPI 330 ASIFAWTRGL340 AHRAKLDNNK350 ELAFFANALE360 EVSIETIEAG370 FMTKDLAACI 380 KGLPNVQRSD390 YLNTFEFMDK400 LGENLKIKLA410 QAK
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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 .ICT or .ICT2 or .ICT3 or :3ICT;style chemicals stick;color identity;select .A:75 or .A:77 or .A:94 or .A:96 or .A:97 or .A:100 or .A:308 or .B:75 or .B:77 or .B:94 or .B:96 or .B:97 or .B:100 or .B:306; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| PDB ID: 6BKX Novel Modes of Inhibition of Wild-Type IDH1: Direct Covalent Modification of His315 with Cmpd1 | ||||||
| Method | X-ray diffraction | Resolution | 1.65 Å | Mutation | No | [5] |
| PDB Sequence |
KKISGGSVVE
12 MQGDEMTRII22 WELIKEKLIF32 PYVELDLHSY42 DLGIENRDAT52 NDQVTKDAAE 62 AIKKHNVGVK72 CATITPDEKR82 VEEFKLKQMW92 KSPNGTIRNI102 LGGTVFREAI 112 ICKNIPRLVS122 GWVKPIIIGR132 HAYGDQYRAT142 DFVVPGPGKV152 EITYTPSDGT 162 QKVTYLVHNF172 EEGGGVAMGM182 YNQDKSIEDF192 AHSSFQMALS202 KGWPLYLSTK 212 NTILKKYDGR222 FKDIFQEIYD232 KQYKSQFEAQ242 KIWYEHRLID252 DMVAQAMKSE 262 GGFIWACKNY272 DGDVQSDSVA282 QGYGSLGMMT292 SVLVCPDGKT302 VEAEAAHGTV 312 TRHYRMYQKG322 QETSTNPIAS332 IFAWTRGLAH342 RAKLDNNKEL352 AFFANALEEV 362 SIETIEAGFM372 TKDLAACIKG382 LPNVQRSDYL392 NTFEFMDKLG402 ENLKIKLAQA 412 KLSLEHH
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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 .ICT or .ICT2 or .ICT3 or :3ICT;style chemicals stick;color identity;select .C:77 or .C:94 or .C:96 or .C:97 or .C:100 or .C:109 or .C:132 or .C:139 or .C:275 or .C:279 or .C:306 or .C:308; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| PDB ID: 6BL2 Novel Modes of Inhibition of Wild-Type IDH1: Direct Covalent Modification of His315 with Cmpd15 | ||||||
| Method | X-ray diffraction | Resolution | 1.92 Å | Mutation | No | [5] |
| PDB Sequence |
KKISGGSVVE
12 MQGDEMTRII22 WELIKEKLIF32 PYVELDLHSY42 DLGIENRDAT52 NDQVTKDAAE 62 AIKKHNVGVK72 CATITPDEKR82 VEEFKLKQMW92 KSPNGTIRNI102 LGGTVFREAI 112 ICKNIPRLVS122 GWVKPIIIGR132 HAYGDQYRAT142 DFVVPGPGKV152 EITYTPSDGT 162 QKVTYLVHNF172 EEGGGVAMGM182 YNQDKSIEDF192 AHSSFQMALS202 KGWPLYLSTK 212 NTILKKYDGR222 FKDIFQEIYD232 KQYKSQFEAQ242 KIWYEHRLID252 DMVAQAMKSE 262 GGFIWACKNY272 DGDVQSDSVA282 QGYGSLGMMT292 SVLVCPDGKT302 VEAEAAHGTV 312 TRHYRMYQKG322 QETSTNPIAS332 IFAWTRGLAH342 RAKLDNNKEL352 AFFANALEEV 362 SIETIEAGFM372 TKDLAACIKG382 LPNVQRSDYL392 NTFEFMDKLG402 ENLKIKLAQA 412 KLSLEH
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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 .ICT or .ICT2 or .ICT3 or :3ICT;style chemicals stick;color identity;select .A:77 or .A:94 or .A:96 or .A:97 or .A:100 or .A:109 or .A:132 or .A:139 or .A:212 or .A:214 or .A:215 or .A:252 or .A:275 or .A:278 or .A:279 or .A:306 or .A:308; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| PDB ID: 6BL1 Novel Modes of Inhibition of Wild-Type IDH1: Direct Covalent Modification of His315 with Cmpd13 | ||||||
| Method | X-ray diffraction | Resolution | 2.02 Å | Mutation | No | [5] |
| PDB Sequence |
KKISGGSVVE
12 MQGDEMTRII22 WELIKEKLIF32 PYVELDLHSY42 DLGIENRDAT52 NDQVTKDAAE 62 AIKKHNVGVK72 CATITPDEKR82 VEEFKLKQMW92 KSPNGTIRNI102 LGGTVFREAI 112 ICKNIPRLVS122 GWVKPIIIGR132 HAYGDQYRAT142 DFVVPGPGKV152 EITYTPSDGT 162 QKVTYLVHNF172 EEGGGVAMGM182 YNQDKSIEDF192 AHSSFQMALS202 KGWPLYLSTK 212 NTILKKYDGR222 FKDIFQEIYD232 KQYKSQFEAQ242 KIWYEHRLID252 DMVAQAMKSE 262 GGFIWACKNY272 DGDVQSDSVA282 QGYGSLGMMT292 SVLVCPDGKT302 VEAEAAHGTV 312 TRHYRMYQKG322 QETSTNPIAS332 IFAWTRGLAH342 RAKLDNNKEL352 AFFANALEEV 362 SIETIEAGFM372 TKDLAACIKG382 LPNVQRSDYL392 NTFEFMDKLG402 ENLKIKLAQA 412 KLSLEH
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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 .ICT or .ICT2 or .ICT3 or :3ICT;style chemicals stick;color identity;select .B:77 or .B:94 or .B:96 or .B:97 or .B:100 or .B:109 or .B:132 or .B:139 or .B:212 or .B:214 or .B:215 or .B:252 or .B:275 or .B:278 or .B:306 or .B:308; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| PDB ID: 6BL0 Novel Modes of Inhibition of Wild-Type IDH1:Direct Covalent Modification of His315 with Cmpd11 | ||||||
| Method | X-ray diffraction | Resolution | 2.17 Å | Mutation | No | [5] |
| PDB Sequence |
KKISGGSVVE
12 MQGDEMTRII22 WELIKEKLIF32 PYVELDLHSY42 DLGIENRDAT52 NDQVTKDAAE 62 AIKKHNVGVK72 CATITPDEKR82 VEEFKLKQMW92 KSPNGTIRNI102 LGGTVFREAI 112 ICKNIPRLVS122 GWVKPIIIGR132 HAYGDQYRAT142 DFVVPGPGKV152 EITYTPSDGT 162 QKVTYLVHNF172 EEGGGVAMGM182 YNQDKSIEDF192 AHSSFQMALS202 KGWPLYLSTK 212 NTILKKYDGR222 FKDIFQEIYD232 KQYKSQFEAQ242 KIWYEHRLID252 DMVAQAMKSE 262 GGFIWACKNY272 DGDVQSDSVA282 QGYGSLGMMT292 SVLVCPDGKT302 VEAEAAHGTV 312 TRHYRMYQKG322 QETSTNPIAS332 IFAWTRGLAH342 RAKLDNNKEL352 AFFANALEEV 362 SIETIEAGFM372 TKDLAACIKG382 LPNVQRSDYL392 NTFEFMDKLG402 ENLKIKLAQA 412 KLSLEH
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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 .ICT or .ICT2 or .ICT3 or :3ICT;style chemicals stick;color identity;select .A:77 or .A:94 or .A:96 or .A:97 or .A:100 or .A:109 or .A:132 or .A:139 or .A:212 or .A:214 or .A:215 or .A:252 or .A:275 or .A:306 or .A:308; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| References | Top | ||||
|---|---|---|---|---|---|
| REF 1 | Transient-State Analysis of Human Isocitrate Dehydrogenase I: Accounting for the Interconversion of Active and Non-Active Conformational States. Biochemistry. 2019 Dec 31;58(52):5366-5380. | ||||
| REF 2 | Structures of human cytosolic NADP-dependent isocitrate dehydrogenase reveal a novel self-regulatory mechanism of activity. J Biol Chem. 2004 Aug 6;279(32):33946-57. | ||||
| REF 3 | Human isocitrate dehydrogenase 1 bound with isocitrate | ||||
| REF 4 | Molecular mechanisms of "off-on switch" of activities of human IDH1 by tumor-associated mutation R132H. Cell Res. 2010 Nov;20(11):1188-200. | ||||
| REF 5 | Novel Modes of Inhibition of Wild-Type Isocitrate Dehydrogenase 1 (IDH1): Direct Covalent Modification of His315. J Med Chem. 2018 Aug 9;61(15):6647-6657. | ||||
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