Target Binding Site Detail

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Target General Information
Ligand General Information
Drug Binding Sites of Target
References
Target General Information  Top
Target ID T88569 Target Info
Target Name Mutated oxalosuccinate decarboxylase (mIDH1)
Synonyms PICD (mutated); Oxalosuccinate decarboxylase (mutated); NADP(+)-specific ICDH (mutated); Isocitrate dehydrogenase [NADP] cytoplasmic (mutated); IDP (mutated); IDH (mutated); Cytosolic NADP-isocitrate dehydrogenase (mutated)
Target Type Clinical trial Target
Gene Name IDH1
Biochemical Class Short-chain dehydrogenases reductase
UniProt ID
IDHC_HUMAN
Ligand General Information  Top
Ligand Name NADP+ Ligand Info
Canonical SMILES C1=CC(=C[N+](=C1)C2C(C(C(O2)COP(=O)(O)OP(=O)(O)OCC3C(C(C(O3)N4C=NC5=C(N=CN=C54)N)OP(=O)(O)O)O)O)O)C(=O)N
InChI 1S/C21H28N7O17P3/c22-17-12-19(25-7-24-17)28(8-26-12)21-16(44-46(33,34)35)14(30)11(43-21)6-41-48(38,39)45-47(36,37)40-5-10-13(29)15(31)20(42-10)27-3-1-2-9(4-27)18(23)32/h1-4,7-8,10-11,13-16,20-21,29-31H,5-6H2,(H7-,22,23,24,25,32,33,34,35,36,37,38,39)/p+1/t10-,11-,13-,14-,15-,16-,20-,21-/m1/s1
InChIKey XJLXINKUBYWONI-NNYOXOHSSA-O
PubChem Compound ID 5886
Drug Binding Sites of Target  Top
PDB ID: 4XS3      Crystal structure of a metabolic reductase with (E)-1-benzyl-5-((1-methyl-5-oxo-2-thioxoimidazolidin-4-ylidene)methyl)pyridin-2(1H)-one
Method X-ray diffraction Resolution 3.29 Å Mutation Yes [1]
PDB Sequence
KKISGGSVVE
12
MQGDEMTRII
22
WELIKEKLIF
32
PYVELDLHSY
42
DLGIENRDAT
52

NDQVTKDAAE
62
AIKKHNVGVK
72
CATITPDEKR
82
VEEFKLKQMW
92
KSPNGTIRNI
102

LGGTVFREAI
112
ICKNIPRKPI
128
IIGHHYRATD
143
FVVPGPGKVE
153
ITYTPSDGTQ
163

KVTYLVHNFE
173
EGGGVAMGMY
183
NQDKSIEDFA
193
HSSFQMALSK
203
GWPLYLSTKN
213

TILKKYDGRF
223
KDIFQEIYDK
233
QYKSQFEAQK
243
IWYEHRLIDD
253
MVAQAMKSEG
263

GFIWACKSLG
289
MMTSVLVCPD
299
GKTVEAEAAH
309
GTVTRHYRMY
319
QKGQETSTNP
329

IASIFAWTRG
339
LAHRAKLDNN
349
KELAFFANAL
359
EEVSIETIEA
369
GFMTKDLAAC
379

IKGLPNVQRS
389
DYLNTFEFMD
399
KLGENLKIKL
409
AQA
Residue
Distance (Å)
GLU17
4.611
ALA74
4.441
THR75
2.653
ILE76
4.051
THR77
3.174
ARG82
2.910
ASN96
4.141
LEU288
3.826
Residue
Distance (Å)
ALA308
3.868
HIS309
3.377
GLY310
2.276
THR311
2.790
VAL312
3.964
THR313
2.745
ARG314
2.322
HIS315
3.203
PDB ID: 5DE1      Crystal structure of human IDH1 in complex with GSK321A
Method X-ray diffraction Resolution 2.25 Å Mutation Yes [2]
PDB Sequence
KKISGGSVVE
12
MQGDEMTRII
22
WELIKEKLIF
32
PYVELDLHSY
42
DLGIENRDAT
52

NDQVTKDAAE
62
AIKKHNVGVK
72
CATITPDEKR
82
VEEFKLKQMW
92
KSPNGTIRNI
102

LGGTVFREAI
112
ICKNIPRLVS
122
GWVKPIIIGH
132
HRATDFVVPG
148
PGKVEITYTP
158

SDGTQKVTYL
168
VHNFEEGGGV
178
AMGMYNQDKS
188
IEDFAHSSFQ
198
MALSKGWPLY
208

LSTKNTILKK
218
YDGRFKDIFQ
228
EIYDKQYKSQ
238
FEAQKIWYEH
248
RLIDDMVAQA
258

MKSEGGFIWA
268
CKNDSVAQGY
285
GSLGMMTSVL
295
VCPDGKTVEA
305
EAAHGTVTRH
315

YRMYQKGQET
325
STNPIASIFA
335
WTRGLAHRAK
345
LDNNKELAFF
355
ANALEEVSIE
365

TIEAGFMTKD
375
LAACIKGLPN
385
VQRSDYLNTF
395
EFMDKLGENL
405
KIKLAQAKL
Residue
Distance (Å)
GLU17
4.670
LYS72
3.596
ALA74
4.030
THR75
3.340
ILE76
3.727
THR77
2.930
ARG82
3.108
ASN96
2.927
SER287
4.235
LEU288
4.883
GLY289
3.916
GLU306
3.528
ALA307
4.099
Residue
Distance (Å)
ALA308
4.954
HIS309
3.475
GLY310
2.929
THR311
3.068
VAL312
2.685
THR313
3.222
ARG314
2.642
HIS315
2.799
SER326
4.472
THR327
3.706
ASN328
2.861
ASP375
3.929
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 [3]
PDB Sequence
KKISGGSVVE
12
MQGDEMTRII
22
WELIKEKLIF
32
PYVELDLHSY
42
DLGIENRDAT
52

NDQVTKDAAE
62
AIKKHNVGVK
72
CATITPDEKR
82
VEEFKLKQMW
92
KSPNGTIRNI
102

LGGTVFREAI
112
ICKNIPRLVS
122
GWVKPIIIGH
132
HARATDFVVP
147
GPGKVEITYT
157

PSDGTQKVTY
167
LVHNFEEGGG
177
VAMGMYNQDK
187
SIEDFAHSSF
197
QMALSKGWPL
207

YLSTKNTILK
217
KYDGRFKDIF
227
QEIYDKQYKS
237
QFEAQKIWYE
247
HRLIDDMVAQ
257

AMKSEGGFIW
267
ACKNVAQGYG
286
SLGMMTSVLV
296
CPDGKTVEAE
306
AAHGTVTRHY
316

RMYQKGQETS
326
TNPIASIFAW
336
TRGLAHRAKL
346
DNNKELAFFA
356
NALEEVSIET
366

IEAGFMTKDL
376
AACIKGLPNV
386
QRSDYLNTFE
396
FMDKLGENLK
406
IKLAQAK
Residue
Distance (Å)
GLU17
4.070
LYS72
3.696
CYS73
4.628
ALA74
3.605
THR75
2.862
ILE76
3.477
THR77
2.930
ARG82
3.142
ASN96
2.986
LEU288
3.364
GLY289
3.432
GLU306
3.429
ALA307
4.069
Residue
Distance (Å)
ALA308
4.097
HIS309
3.206
GLY310
2.856
THR311
2.869
VAL312
2.513
THR313
2.882
ARG314
2.136
HIS315
2.718
SER326
4.039
THR327
3.412
ASN328
2.716
ASP375
3.748
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 [3]
PDB Sequence
> Chain A
KKISGGSVVE
12
MQGDEMTRII
22
WELIKEKLIF
32
PYVELDLHSY
42
DLGIENRDAT
52

NDQVTKDAAE
62
AIKKHNVGVK
72
CATITPDEKR
82
VEEFKLKQMW
92
KSPNGTIRNI
102

LGGTVFREAI
112
ICKNIPRLVS
122
GWVKPIIIGH
132
HARATDFVVP
147
GPGKVEITYT
157

PSDGTQKVTY
167
LVHNFEEGGG
177
VAMGMYNQDK
187
SIEDFAHSSF
197
QMALSKGWPL
207

YLSTKNTILK
217
KYDGRFKDIF
227
QEIYDKQYKS
237
QFEAQKIWYE
247
HRLIDDMVAQ
257

AMKSEGGFIW
267
ACKNGSLGMM
291
TSVLVCPDGK
301
TVEAEAAHGT
311
VTRHYRMYQK
321

GQETSTNPIA
331
SIFAWTRGLA
341
HRAKLDNNKE
351
LAFFANALEE
361
VSIETIEAGF
371

MTKDLAACIK
381
GLPNVQRSDY
391
LNTFEFMDKL
401
GENLKIKLAQ
411
AKL
> Chain B
KKISGGSVVE
12
MQGDEMTRII
22
WELIKEKLIF
32
PYVELDLHSY
42
DLGIENRDAT
52

NDQVTKDAAE
62
AIKKHNVGVK
72
CATITPDEKR
82
VEEFKLKQMW
92
KSPNGTIRNI
102

LGGTVFREAI
112
ICKNIPRLVS
122
GWVKPIIIGR
132
HARATDFVVP
147
GPGKVEITYT
157

PSDGTQKVTY
167
LVHNFEEGGG
177
VAMGMYNQDK
187
SIEDFAHSSF
197
QMALSKGWPL
207

YLSTKNTILK
217
KYDGRFKDIF
227
QEIYDKQYKS
237
QFEAQKIWYE
247
HRLIDDMVAQ
257

AMKSEGGFIW
267
ACKNYGSLGM
290
MTSVLVCPDG
300
KTVEAEAAHG
310
TVTRHYRMYQ
320

KGQETSTNPI
330
ASIFAWTRGL
340
AHRAKLDNNK
350
ELAFFANALE
360
EVSIETIEAG
370

FMTKDLAACI
380
KGLPNVQRSD
390
YLNTFEFMDK
400
LGENLKIKLA
410
QAK
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .NAP or .NAP2 or .NAP3 or :3NAP;style chemicals stick;color identity;select .A:17 or .A:72 or .A:74 or .A:75 or .A:76 or .A:77 or .A:82 or .A:95 or .A:96 or .A:288 or .A:289 or .A:306 or .A:308 or .A:309 or .A:310 or .A:311 or .A:312 or .A:313 or .A:314 or .A:315 or .A:326 or .A:327 or .A:328 or .A:375 or .A:260 or .B:17 or .B:72 or .B:74 or .B:75 or .B:76 or .B:77 or .B:82 or .B:96 or .B:288 or .B:289 or .B:306 or .B:307 or .B:309 or .B:310 or .B:311 or .B:312 or .B:313 or .B:314 or .B:315 or .B:326 or .B:327 or .B:328 or .B:329 or .B:375; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue [Chain]
Distance (Å)
GLU17[A]
4.474
LYS72[A]
3.253
ALA74[A]
3.705
THR75[A]
2.030
ILE76[A]
3.842
THR77[A]
3.125
ARG82[A]
2.812
PRO95[A]
4.960
ASN96[A]
3.303
LEU288[A]
3.973
GLY289[A]
4.061
GLU306[A]
4.362
ALA308[A]
4.873
HIS309[A]
3.747
GLY310[A]
3.176
THR311[A]
3.117
VAL312[A]
2.494
THR313[A]
2.940
ARG314[A]
2.646
HIS315[A]
2.772
SER326[A]
4.106
THR327[A]
3.695
ASN328[A]
3.119
ASP375[A]
4.179
LYS260[A]
4.478
Residue [Chain]
Distance (Å)
GLU17[B]
4.786
LYS72[B]
3.512
ALA74[B]
3.883
THR75[B]
3.058
ILE76[B]
3.757
THR77[B]
2.819
ARG82[B]
3.009
ASN96[B]
2.594
LEU288[B]
3.757
GLY289[B]
3.667
GLU306[B]
3.936
ALA307[B]
4.229
HIS309[B]
3.348
GLY310[B]
3.034
THR311[B]
3.017
VAL312[B]
2.680
THR313[B]
2.943
ARG314[B]
2.543
HIS315[B]
2.519
SER326[B]
4.425
THR327[B]
3.600
ASN328[B]
2.721
PRO329[B]
4.904
ASP375[B]
4.055
PDB ID: 3MAR      Crystal structure of homodimeric R132H mutant of human cytosolic NADP(+)-dependent isocitrate dehydrogenase in complex with NADP
Method X-ray diffraction Resolution 3.41 Å Mutation Yes [3]
PDB Sequence
SKKISGGSVV
11
EMQGDEMTRI
21
IWELIKEKLI
31
FPYVELDLHS
41
YDLGIENRDA
51

TNDQVTKDAA
61
EAIKKHNVGV
71
KCATITPDEK
81
RVEEFKLKQM
91
WKSPNGTIRN
101

ILGGTVFREA
111
IICKNIPRLV
121
SGWVKPIIIG
131
HHAATDFVVP
147
GPGKVEITYT
157

PSDGTQKVTY
167
LVHNFEEGGG
177
VAMGMYNQDK
187
SIEDFAHSSF
197
QMALSKGWPL
207

YLSTKNTILK
217
KYDGRFKDIF
227
QEIYDKQYKS
237
QFEAQKIWYE
247
HRLIDDMVAQ
257

ASEGGFIWAC
269
KNGYGSLGMM
291
TSVLVCPDGK
301
TVEAEAAHGT
311
VTRHYRMYQK
321

GQETSTNPIA
331
SIFAWTRGLA
341
HRAKLDNNKE
351
LAFFANALEE
361
VSIETIEAGF
371

MTKDLAACIK
381
GLPNVQRSDY
391
LNTFEFMDKL
401
GENLKIKLAQ
411
AKL
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .NAP or .NAP2 or .NAP3 or :3NAP;style chemicals stick;color identity;select .A:17 or .A:72 or .A:74 or .A:75 or .A:76 or .A:77 or .A:82 or .A:96 or .A:288 or .A:289 or .A:306 or .A:307 or .A:308 or .A:309 or .A:310 or .A:311 or .A:312 or .A:313 or .A:314 or .A:315 or .A:326 or .A:327 or .A:328 or .A:329 or .A:375; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
GLU17
4.924
LYS72
3.278
ALA74
4.140
THR75
3.064
ILE76
3.690
THR77
3.218
ARG82
3.107
ASN96
3.816
LEU288
3.791
GLY289
3.869
GLU306
3.618
ALA307
4.527
ALA308
4.489
Residue
Distance (Å)
HIS309
3.018
GLY310
3.353
THR311
2.461
VAL312
2.829
THR313
3.262
ARG314
2.915
HIS315
2.620
SER326
4.604
THR327
3.461
ASN328
2.519
PRO329
4.645
ASP375
3.621
PDB ID: 4UMX      IDH1 R132H in complex with cpd 1
Method X-ray diffraction Resolution 1.88 Å Mutation Yes [4]
PDB Sequence
KKISGGSVVE
12
MQGDEMTRII
22
WELIKEKLIF
32
PYVELDLHSY
42
DLGIENRDAT
52

NDQVTKDAAE
62
AIKKHNVGVK
72
CATITPDEKR
82
VEEFKLKQMW
92
KSPNGTIRNI
102

LGGTVFREAI
112
ICKNIPRLVS
122
GWVKPIIIGH
132
HAYGDQYRAT
142
DFVVPGPGKV
152

EITYTPSDGT
162
QKVTYLVHNF
172
EEGGGVAMGM
182
YNQDKSIEDF
192
AHSSFQMALS
202

KGWPLYLSTK
212
NTILKKYDGR
222
FKDIFQEIYD
232
KQYKSQFEAQ
242
KIWYEHRLID
252

DMVAQAMKSE
262
GGFIWACKNY
272
DGDVQSDSVA
282
QGYGSLGMMT
292
SVLVCPDGKT
302

VEAEAAHGTV
312
TRHYRMYQKG
322
QETSTNPIAS
332
IFAWTRGLAH
342
RAKLDNNKEL
352

AFFANALEEV
362
SIETIEAGFM
372
TKDLAACIKG
382
LPNVQRSDYL
392
NTFEFMDKLG
402

ENLKIKLAQA
412
KL
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .NAP or .NAP2 or .NAP3 or :3NAP;style chemicals stick;color identity;select .A:17 or .A:72 or .A:73 or .A:74 or .A:75 or .A:76 or .A:77 or .A:82 or .A:96 or .A:277 or .A:287 or .A:288 or .A:289 or .A:306 or .A:307 or .A:309 or .A:310 or .A:311 or .A:312 or .A:313 or .A:314 or .A:315 or .A:326 or .A:327 or .A:328 or .A:375; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
GLU17
4.609
LYS72
3.421
CYS73
4.831
ALA74
3.502
THR75
2.904
ILE76
3.616
THR77
3.009
ARG82
3.005
ASN96
3.124
GLN277
3.397
SER287
4.642
LEU288
3.745
GLY289
3.668
Residue
Distance (Å)
GLU306
4.527
ALA307
4.364
HIS309
3.313
GLY310
2.863
THR311
3.074
VAL312
2.758
THR313
3.246
ARG314
2.568
HIS315
2.783
SER326
4.401
THR327
3.806
ASN328
2.878
ASP375
3.971
PDB ID: 4UMY      IDH1 R132H in complex with cpd 1
Method X-ray diffraction Resolution 2.07 Å Mutation Yes [4]
PDB Sequence
KKISGGSVVE
12
MQGDEMTRII
22
WELIKEKLIF
32
PYVELDLHSY
42
DLGIENRDAT
52

NDQVTKDAAE
62
AIKKHNVGVK
72
CATITPDEKR
82
VEEFKLKQMW
92
KSPNGTIRNI
102

LGGTVFREAI
112
ICKNIPRLVS
122
GWVKPIIIGH
132
HRATDFVVPG
148
PGKVEITYTP
158

SDGTQKVTYL
168
VHNFEEGGGV
178
AMGMYNQDKS
188
IEDFAHSSFQ
198
MALSKGWPLY
208

LSTKNTILKK
218
YDGRFKDIFQ
228
EIYDKQYKSQ
238
FEAQKIWYEH
248
RLIDDMVAQA
258

MKSEGGFIWA
268
CKNGSLGMMT
292
SVLVCPDGKT
302
VEAEAAHGTV
312
TRHYRMYQKG
322

QETSTNPIAS
332
IFAWTRGLAH
342
RAKLDNNKEL
352
AFFANALEEV
362
SIETIEAGFM
372

TKDLAACIKG
382
LPNVQRSDYL
392
NTFEFMDKLG
402
ENLKIKLAQA
412
K
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .NAP or .NAP2 or .NAP3 or :3NAP;style chemicals stick;color identity;select .A:17 or .A:72 or .A:73 or .A:74 or .A:75 or .A:76 or .A:77 or .A:82 or .A:96 or .A:288 or .A:289 or .A:306 or .A:307 or .A:308 or .A:309 or .A:310 or .A:311 or .A:312 or .A:313 or .A:314 or .A:315 or .A:326 or .A:327 or .A:328 or .A:375; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
GLU17
4.607
LYS72
3.520
CYS73
4.848
ALA74
3.473
THR75
2.964
ILE76
3.628
THR77
2.964
ARG82
2.983
ASN96
3.328
LEU288
3.646
GLY289
3.715
GLU306
3.320
ALA307
4.134
Residue
Distance (Å)
ALA308
4.404
HIS309
3.296
GLY310
2.869
THR311
3.121
VAL312
2.774
THR313
3.231
ARG314
2.714
HIS315
2.808
SER326
4.544
THR327
3.689
ASN328
2.830
ASP375
4.086
PDB ID: 6U4J      Crystal structure of IDH1 R132H mutant in complex with FT-2102
Method X-ray diffraction Resolution 2.11 Å Mutation Yes [5]
PDB Sequence
KKISGGSVVE
12
MQGDEMTRII
22
WELIKEKLIF
32
PYVELDLHSY
42
DLGIENRDAT
52

NDQVTKDAAE
62
AIKKHNVGVK
72
CATITPDEKR
82
VEEFKLKQMW
92
KSPNGTIRNI
102

LGGTVFREAI
112
ICKNIPRLVS
122
GWVKPIIIGH
132
HAYGDQYRAT
142
DFVVPGPGKV
152

EITYTPSDGT
162
QKVTYLVHNF
172
EEGGGVAMGM
182
YNQDKSIEDF
192
AHSSFQMALS
202

KGWPLYLSTK
212
NTILKKYDGR
222
FKDIFQEIYD
232
KQYKSQFEAQ
242
KIWYEHRLID
252

DMVAQAMKSE
262
GGFIWACKNY
272
DGDVQSDSVA
282
QGYGSLGMMT
292
SVLVCPDGKT
302

VEAEAAHGTV
312
TRHYRMYQKG
322
QETSTNPIAS
332
IFAWTRGLAH
342
RAKLDNNKEL
352

AFFANALEEV
362
SIETIEAGFM
372
TKDLAACIKG
382
LPNVQRSDYL
392
NTFEFMDKLG
402

ENLKIKLAQA
412
KLSLE
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .NAP or .NAP2 or .NAP3 or :3NAP;style chemicals stick;color identity;select .A:17 or .A:72 or .A:73 or .A:74 or .A:75 or .A:76 or .A:77 or .A:82 or .A:96 or .A:277 or .A:287 or .A:288 or .A:289 or .A:306 or .A:307 or .A:308 or .A:309 or .A:310 or .A:311 or .A:312 or .A:313 or .A:314 or .A:315 or .A:326 or .A:327 or .A:328 or .A:375; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
GLU17
4.831
LYS72
3.505
CYS73
4.893
ALA74
3.651
THR75
3.193
ILE76
3.501
THR77
2.959
ARG82
3.223
ASN96
2.894
GLN277
4.511
SER287
4.166
LEU288
4.107
GLY289
3.740
GLU306
3.309
Residue
Distance (Å)
ALA307
3.170
ALA308
3.570
HIS309
2.888
GLY310
2.816
THR311
2.932
VAL312
2.748
THR313
3.550
ARG314
2.724
HIS315
2.884
SER326
4.350
THR327
3.902
ASN328
2.926
ASP375
4.172
PDB ID: 4KZO      Crystal Structure Analysis of human IDH1 mutants in complex with NADP+ and Ca2+/alpha-Ketoglutarate
Method X-ray diffraction Resolution 2.20 Å Mutation Yes [6]
PDB Sequence
KKISGGSVVE
12
MQGDEMTRII
22
WELIKEKLIF
32
PYVELDLHSY
42
DLGIENRDAT
52

NDQVTKDAAE
62
AIKKHNVGVK
72
CATITPDEKR
82
VEEFKLKQMW
92
KSPNGTIRNI
102

LGGTVFREAI
112
ICKNIPRLVS
122
GWVKPIIIGH
132
HAYGDQYRAT
142
DFVVPGPGKV
152

EITYTPSDGT
162
QKVTYLVHNF
172
EEGGGVAMGM
182
YNQDKSIEDF
192
AHSSFQMALS
202

KGWPLYLSTK
212
NTILKKYDGR
222
FKDIFQEIYD
232
KQYKSQFEAQ
242
KIWYEHRLID
252

DMVAQAMKSE
262
GGFIWACKNY
272
DGDVQSDSVA
282
QGYGSLGMMT
292
SVLVCPDGKT
302

VEAEAAHGTV
312
TRHYRMYQKG
322
QETSTNPIAS
332
IFAWTRGLAH
342
RAKLDNNKEL
352

AFFANALEEV
362
SIETIEAGFM
372
TKDLAACIKG
382
LPNVQRSDYL
392
NTFEFMDKLG
402

ENLKIKLAQA
412
KLSL
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .NAP or .NAP2 or .NAP3 or :3NAP;style chemicals stick;color identity;select .A:17 or .A:72 or .A:73 or .A:74 or .A:75 or .A:76 or .A:77 or .A:82 or .A:96 or .A:100 or .A:287 or .A:288 or .A:289 or .A:306 or .A:307 or .A:308 or .A:309 or .A:310 or .A:311 or .A:312 or .A:313 or .A:314 or .A:315 or .A:326 or .A:327 or .A:328 or .A:375; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
GLU17
4.636
LYS72
3.379
CYS73
4.719
ALA74
3.473
THR75
2.937
ILE76
3.677
THR77
3.200
ARG82
3.148
ASN96
2.811
ARG100
4.938
SER287
4.943
LEU288
3.549
GLY289
3.951
GLU306
4.686
Residue
Distance (Å)
ALA307
3.278
ALA308
3.353
HIS309
3.184
GLY310
2.936
THR311
3.026
VAL312
2.586
THR313
3.359
ARG314
2.547
HIS315
2.863
SER326
4.741
THR327
3.640
ASN328
2.889
ASP375
4.316
PDB ID: 4L06      Crystal Structure Analysis of human IDH1 mutants in complex with NADP+ and Ca2+/alpha-Ketoglutarate
Method X-ray diffraction Resolution 2.28 Å Mutation Yes [6]
PDB Sequence
KKISGGSVVE
12
MQGDEMTRII
22
WELIKEKLIF
32
PYVELDLHSY
42
DLGIENRDAT
52

NDQVTKDAAE
62
AIKKHNVGVK
72
CATITPDEKR
82
VEEFKLKQMW
92
KSPNGTIRNI
102

LGGTVFREAI
112
ICKNIPRLVS
122
GWVKPIIIGR
132
HAYGDQDRAT
142
DFVVPGPGKV
152

EITYTPSDGT
162
QKVTYLVHNF
172
EEGGGVAMGM
182
YNQDKSIEDF
192
AHSSFQMALS
202

KGWPLYLSTK
212
NTILKKYDGR
222
FKDIFQEIYD
232
KQYKSQFEAQ
242
KIWYEHRLID
252

DMVAQAMKSE
262
GGFIWACKNY
272
DGDVQSDSVA
282
QGYGSLGMMT
292
SVLVCPDGKT
302

VEAEAAHGTV
312
TRHYRMYQKG
322
QETSTNPIAS
332
IFAWTRGLAH
342
RAKLDNNKEL
352

AFFANALEEV
362
SIETIEAGFM
372
TKDLAACIKG
382
LPNVQRSDYL
392
NTFEFMDKLG
402

ENLKIKLAQA
412
KLS
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .NAP or .NAP2 or .NAP3 or :3NAP;style chemicals stick;color identity;select .A:17 or .A:72 or .A:73 or .A:74 or .A:75 or .A:76 or .A:77 or .A:82 or .A:96 or .A:288 or .A:289 or .A:306 or .A:307 or .A:308 or .A:309 or .A:310 or .A:311 or .A:312 or .A:313 or .A:314 or .A:315 or .A:326 or .A:327 or .A:328 or .A:375; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
GLU17
4.797
LYS72
3.416
CYS73
4.676
ALA74
3.328
THR75
2.751
ILE76
3.654
THR77
3.182
ARG82
3.343
ASN96
2.855
LEU288
3.583
GLY289
3.835
GLU306
4.074
ALA307
3.468
Residue
Distance (Å)
ALA308
3.859
HIS309
3.163
GLY310
2.767
THR311
3.187
VAL312
2.910
THR313
3.467
ARG314
2.442
HIS315
3.103
SER326
4.735
THR327
3.787
ASN328
2.942
ASP375
4.439
PDB ID: 6O2Z      Crystal structure of IDH1 R132H mutant in complex with compound 32
Method X-ray diffraction Resolution 2.50 Å Mutation Yes [7]
PDB Sequence
KKISGGSVVE
12
MQGDEMTRII
22
WELIKEKLIF
32
PYVELDLHSY
42
DLGIENRDAT
52

NDQVTKDAAE
62
AIKKHNVGVK
72
CATITPDEKR
82
VEEFKLKQMW
92
KSPNGTIRNI
102

LGGTVFREAI
112
ICKNIPRLVS
122
GWVKPIIIGH
132
HADQYRATDF
144
VVPGPGKVEI
154

TYTPSDGTQK
164
VTYLVHNFEE
174
GGGVAMGMYN
184
QDKSIEDFAH
194
SSFQMALSKG
204

WPLYLSTKNT
214
ILKKYDGRFK
224
DIFQEIYDKQ
234
YKSQFEAQKI
244
WYEHRLIDDM
254

VAQAMKSEGG
264
FIWACKNYDG
274
DVQSDSVAQG
284
YGSLGMMTSV
294
LVCPDGKTVE
304

AEAAHGTVTR
314
HYRMYQKGQE
324
TSTNPIASIF
334
AWTRGLAHRA
344
KLDNNKELAF
354

FANALEEVSI
364
ETIEAGFMTK
374
DLAACIKGLP
384
NVQRSDYLNT
394
FEFMDKLGEN
404

LKIKLAQAKL
414
S
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .NAP or .NAP2 or .NAP3 or :3NAP;style chemicals stick;color identity;select .A:17 or .A:72 or .A:73 or .A:74 or .A:75 or .A:76 or .A:77 or .A:82 or .A:96 or .A:277 or .A:287 or .A:288 or .A:289 or .A:306 or .A:307 or .A:308 or .A:309 or .A:310 or .A:311 or .A:312 or .A:313 or .A:314 or .A:315 or .A:326 or .A:327 or .A:328 or .A:375; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
GLU17
4.658
LYS72
3.413
CYS73
4.822
ALA74
3.577
THR75
3.064
ILE76
3.676
THR77
2.913
ARG82
3.029
ASN96
2.940
GLN277
3.815
SER287
4.113
LEU288
4.327
GLY289
3.663
GLU306
3.700
Residue
Distance (Å)
ALA307
4.230
ALA308
4.931
HIS309
3.287
GLY310
2.709
THR311
3.080
VAL312
2.768
THR313
3.192
ARG314
2.684
HIS315
2.925
SER326
4.773
THR327
3.720
ASN328
3.009
ASP375
4.094
PDB ID: 5LGE      Crystal Structure of human IDH1 mutant (R132H) in complex with NADP+ and an Inhibitor related to BAY 1436032
Method X-ray diffraction Resolution 2.70 Å Mutation Yes [8]
PDB Sequence
KKISGGSVVE
12
MQGDEMTRII
22
WELIKEKLIF
32
PYVELDLHSY
42
DLGIENRDAT
52

NDQVTKDAAE
62
AIKKHNVGVK
72
CATITPDEKR
82
VEEFKLKQMW
92
KSPNGTIRNI
102

LGGTVFREAI
112
ICKNIPRLVS
122
GWVKPIIIGH
132
HAYGDQYRAT
142
DFVVPGPGKV
152

EITYTPTYLH
170
NFEEGGGVAM
180
GMYNQDKSIE
190
DFAHSSFQMA
200
LSKGWPLYLS
210

TKNTILKKYD
220
GRFKDIFQEI
230
YDKQYKSQFE
240
AQKIWYEHRL
250
IDDMVAQAMK
260

SEGGFIWACK
270
NYDGDVQSDS
280
VAQGYGSLGM
290
MTSVLVCPDG
300
KTVEAEAAHG
310

TVTRHYRMYQ
320
KGQETSTNPI
330
ASIFAWTRGL
340
AHRAKLDNNK
350
ELAFFANALE
360

EVSIETIEAG
370
FMTKDLAACI
380
KGLPNVQRSD
390
YLNTFEFMDK
400
LGENLKIKLA
410

QAKLSL
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .NAP or .NAP2 or .NAP3 or :3NAP;style chemicals stick;color identity;select .A:17 or .A:72 or .A:73 or .A:74 or .A:75 or .A:76 or .A:77 or .A:82 or .A:96 or .A:288 or .A:289 or .A:306 or .A:307 or .A:308 or .A:309 or .A:310 or .A:311 or .A:312 or .A:313 or .A:314 or .A:315 or .A:326 or .A:327 or .A:328 or .A:375; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
GLU17
4.623
LYS72
3.464
CYS73
4.850
ALA74
3.659
THR75
2.918
ILE76
3.782
THR77
3.422
ARG82
3.341
ASN96
2.973
LEU288
3.502
GLY289
3.802
GLU306
2.947
ALA307
3.561
Residue
Distance (Å)
ALA308
4.363
HIS309
3.106
GLY310
2.943
THR311
3.118
VAL312
2.710
THR313
3.410
ARG314
2.641
HIS315
2.740
SER326
4.087
THR327
3.759
ASN328
2.861
ASP375
3.974
PDB ID: 6O2Y      Crystal structure of IDH1 R132H mutant in complex with compound 24
Method X-ray diffraction Resolution 2.80 Å Mutation Yes [7]
PDB Sequence
KKISGGSVVE
12
MQGDEMTRII
22
WELIKEKLIF
32
PYVELDLHSY
42
DLGIENRDAT
52

NDQVTKDAAE
62
AIKKHNVGVK
72
CATITPDEKR
82
VEEFKLKQMW
92
KSPNGTIRNI
102

LGGTVFREAI
112
ICKNIPRLVS
122
GWVKPIIIGH
132
HAYGDQYRAT
142
DFVVPGPGKV
152

EITYTPSDGT
162
QKVTYLVHNF
172
EEGGGVAMGM
182
YNQDKSIEDF
192
AHSSFQMALS
202

KGWPLYLSTK
212
NTILKKYDGR
222
FKDIFQEIYD
232
KQYKSQFEAQ
242
KIWYEHRLID
252

DMVAQAMKSE
262
GGFIWACKNY
272
DGDVQSDSVA
282
QGYGSLGMMT
292
SVLVCPDGKT
302

VEAEAAHGTV
312
TRHYRMYQKG
322
QETSTNPIAS
332
IFAWTRGLAH
342
RAKLDNNKEL
352

AFFANALEEV
362
SIETIEAGFM
372
TKDLAACIKG
382
LPNVQRSDYL
392
NTFEFMDKLG
402

ENLKIKLAQA
412
KLE
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .NAP or .NAP2 or .NAP3 or :3NAP;style chemicals stick;color identity;select .A:17 or .A:72 or .A:73 or .A:74 or .A:75 or .A:76 or .A:77 or .A:82 or .A:96 or .A:277 or .A:288 or .A:289 or .A:306 or .A:307 or .A:308 or .A:309 or .A:310 or .A:311 or .A:312 or .A:313 or .A:314 or .A:315 or .A:326 or .A:327 or .A:328 or .A:375; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
GLU17
4.634
LYS72
3.662
CYS73
4.643
ALA74
3.154
THR75
2.847
ILE76
3.586
THR77
3.485
ARG82
3.029
ASN96
2.841
GLN277
3.842
LEU288
3.982
GLY289
3.640
GLU306
3.553
Residue
Distance (Å)
ALA307
4.893
ALA308
4.004
HIS309
3.380
GLY310
2.968
THR311
2.889
VAL312
2.718
THR313
3.324
ARG314
2.571
HIS315
3.019
SER326
4.342
THR327
3.938
ASN328
2.943
ASP375
4.071
References  Top
REF 1 Inhibition of Cancer-Associated Mutant Isocitrate Dehydrogenases by 2-Thiohydantoin Compounds. J Med Chem. 2015 Sep 10;58(17):6899-6908.
REF 2 New IDH1 mutant inhibitors for treatment of acute myeloid leukemia. Nat Chem Biol. 2015 Nov;11(11):878-86.
REF 3 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 4 Selective inhibition of mutant isocitrate dehydrogenase 1 (IDH1) via disruption of a metal binding network by an allosteric small molecule. J Biol Chem. 2015 Jan 9;290(2):762-74.
REF 5 Structure-Based Design and Identification of FT-2102 (Olutasidenib), a Potent Mutant-Selective IDH1 Inhibitor. J Med Chem. 2020 Feb 27;63(4):1612-1623.
REF 6 Mutant IDH1 enhances the production of 2-hydroxyglutarate due to its kinetic mechanism. Biochemistry. 2013 Jul 2;52(26):4563-77.
REF 7 Discovery and Optimization of Quinolinone Derivatives as Potent, Selective, and Orally Bioavailable Mutant Isocitrate Dehydrogenase 1 (mIDH1) Inhibitors. J Med Chem. 2019 Jul 25;62(14):6575-6596.
REF 8 Pan-mutant IDH1 inhibitor BAY 1436032 for effective treatment of IDH1 mutant astrocytoma in vivo. Acta Neuropathol. 2017 Apr;133(4):629-644.

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