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 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
IDHC_HUMAN
Ligand General Information  Top
Ligand Name NADPH Ligand Info
Canonical SMILES C1C=CN(C=C1C(=O)N)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
InChI 1S/C21H30N7O17P3/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/h1,3-4,7-8,10-11,13-16,20-21,29-31H,2,5-6H2,(H2,23,32)(H,36,37)(H,38,39)(H2,22,24,25)(H2,33,34,35)/t10-,11-,13-,14-,15-,16-,20-,21-/m1/s1
InChIKey ACFIXJIJDZMPPO-NNYOXOHSSA-N
PubChem Compound ID 5884
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
QGDEMTRIIW
23
ELIKEKLIFP
33
YVELDLHSYD
43
LGIENRDATN
53

DQVTKDAAEA
63
IKKHNVGVKC
73
ATITPDEKRV
83
EEFKLKQMWK
93
SPNGTIRNIL
103

GGTVFREAII
113
CKNIPRLVSG
123
WVKPIIIGRH
133
AYGDQYRATD
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
GFIWACKNYD
273
GDVQSDSVAQ
283
GYGSLGMMTS
293
VLVCPDGKTV
303

EAEAAHGTVT
313
RHYRMYQKGQ
323
ETSTNPIASI
333
FAWTRGLAHR
343
AKLDNNKELA
353

FFANALEEVS
363
IETIEAGFMT
373
KDLAACIKGL
383
PNVQRSDYLN
393
TFEFMDKLGE
403

NLKIKLAQA
Residue
Distance (Å)
GLU17
3.847
ILE22
4.923
ALA74
4.814
THR75
2.441
ILE76
2.823
THR77
2.511
ARG82
2.509
GLN283
4.893
SER287
4.649
LEU288
2.511
GLY289
3.305
HIS309
2.565
Residue
Distance (Å)
GLY310
1.964
THR311
2.283
VAL312
1.908
THR313
2.913
ARG314
2.841
HIS315
2.877
SER326
4.366
THR327
2.963
ASN328
2.015
PRO329
4.104
ALA331
4.438
ASP375
2.778
PDB ID: 6IO0      Human IDH1 R132C mutant complexed with compound A.
Method X-ray diffraction Resolution 2.20 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
GWVKPIIIGC
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
CKVQSDSVAQ
283
GYGSLGMMTS
293
VLVCPDGKTV
303
EAEAAHGTVT
313

RHYRMYQKGQ
323
ETSTNPIASI
333
FAWTRGLAHR
343
AKLDNNKELA
353
FFANALEEVS
363

IETIEAGFMT
373
KDLAACIKGL
383
PNVQRSDYLN
393
TFEFMDKLGE
403
NLKIKLAQAK
413
Residue
Distance (Å)
GLU17
4.704
LYS72
3.352
CYS73
4.607
ALA74
3.502
THR75
2.920
ILE76
3.796
THR77
2.985
ARG82
3.216
ASN96
3.363
GLN283
4.094
LEU288
3.761
GLY289
4.002
GLU306
3.088
ALA307
3.876
Residue
Distance (Å)
ALA308
4.278
HIS309
3.428
GLY310
2.846
THR311
3.099
VAL312
2.843
THR313
3.133
ARG314
4.166
HIS315
3.036
SER326
4.372
THR327
3.539
ASN328
2.725
PRO329
4.959
ASP375
3.843
PDB ID: 5L57      Crystal structure of Iso-citrate Dehydrogenase R132H in complex with a novel inhibitor (compound 13a)
Method X-ray diffraction Resolution 2.69 Å Mutation Yes [3]
PDB Sequence
KKISGGSVVE
12
MQGDEMTRII
22
WELIKEKLIF
32
PYVELDLHSY
42
DLGIENRDAT
52

NDQVTKDAAE
62
AIKKHNVGVK
72
CATITPDAAR
82
VEEFKLKQMW
92
KSPNGTIRNI
102

LGGTVFREAI
112
ICKNIPRLVS
122
GWVKPIIIGH
132
HAYGDQYRAT
142
DFVVPGPGKV
152

EITYTPSDGT
162
TYLVHNFEEG
175
GGVAMGMYNQ
185
DKSIEDFAHS
195
SFQMALSKGW
205

PLYLSTKNTI
215
LKKYDGRFKD
225
IFQEIYDKQY
235
KSQFAAAAIW
245
YEHRLIDDMV
255

AQAMKSEGGF
265
IWACKNYDGD
275
VQSDSVAQGY
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)
LYS72
4.348
ALA74
4.042
THR75
2.883
ILE76
3.427
THR77
2.897
ARG82
3.052
ASN96
3.156
ASP279
3.630
SER280
3.431
GLN283
4.601
LEU288
3.409
GLY289
3.879
GLU306
2.928
Residue
Distance (Å)
ALA307
4.357
HIS309
3.383
GLY310
2.980
THR311
3.107
VAL312
2.845
THR313
3.500
ARG314
2.771
HIS315
3.294
SER326
4.368
THR327
3.841
ASN328
3.060
ASP375
4.136
PDB ID: 5L58      Crystal structure of Iso-citrate Dehydrogenase 1 [IDH1 (R132H)] in complex with a novel inhibitor (Compound 2)
Method X-ray diffraction Resolution 3.04 Å Mutation Yes [3]
PDB Sequence
KKISGGSVVE
12
MQGDEMTRII
22
WELIKEKLIF
32
PYVELDLHSY
42
DLGIENRDAT
52

NDQVTKDAAE
62
AIKKHNVGVK
72
CATITPDAAR
82
VEEFKLKQMW
92
KSPNGTIRNI
102

LGGTVFREAI
112
ICKNIPRLVS
122
GWVKPIIIGH
132
HAYGATDFVV
146
PGPEITTYLV
169

GGVAMGMYNQ
185
DKSIEDFAHS
195
SFQMALSKGW
205
PLYLSTKKYD
220
GRFKDIFQEI
230

YDKQYKSQFA
240
AAAIWYEHRL
250
IDDMVAQAMK
260
SEGGFIWACK
270
NYVAQGYGSL
288

GMMTSVLVCP
298
DGKTVEAEAA
308
HGTVTRHYRM
318
YQKGQETSTN
328
PIASIFAWTR
338

GLAHRAKLDN
348
NKELAFFANA
358
LEEVSIETIE
368
AGFMTKDLAA
378
CIKGLPNVQR
388

SDYLNTFEFM
398
DKLGENLKIK
408
LAQAKL
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .NDP or .NDP2 or .NDP3 or :3NDP;style chemicals stick;color identity;select .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:281 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)
LYS72
3.341
CYS73
4.754
ALA74
3.962
THR75
3.050
ILE76
3.904
THR77
2.951
ARG82
3.595
ASN96
3.057
VAL281
4.453
LEU288
3.517
GLY289
3.513
GLU306
3.325
ALA307
3.923
Residue
Distance (Å)
ALA308
3.865
HIS309
3.261
GLY310
3.114
THR311
3.040
VAL312
2.687
THR313
3.483
ARG314
1.297
HIS315
3.033
SER326
4.026
THR327
3.848
ASN328
2.954
ASP375
3.681
PDB ID: 4XRX      Crystal structure of a metabolic reductase with (E)-5-((1-methyl-5-oxo-2-thioxoimidazolidin-4-ylidene)methyl)pyridin-2(1H)-one
Method X-ray diffraction Resolution 3.20 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
HYRATDFVVP
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
ACKSLGMMTS
293
VLVCPDGKTV
303
EAEAAHGTVT
313
RHYRMYQKGQ
323

ETSTNPIASI
333
FAWTRGLAHR
343
AKLDNNKELA
353
FFANALEEVS
363
IETIEAGFMT
373

KDLAACIKGL
383
PNVQRSDYLN
393
TFEFMDKLGE
403
NLKIKLAQAK
413
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .NDP or .NDP2 or .NDP3 or :3NDP;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:375; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
GLU17
4.765
LYS72
3.094
ALA74
3.934
THR75
2.925
ILE76
3.925
THR77
3.040
ARG82
3.425
ASN96
3.669
LEU288
3.395
GLY289
3.842
GLU306
3.974
ALA307
4.442
Residue
Distance (Å)
ALA308
4.135
HIS309
3.292
GLY310
2.591
THR311
3.078
VAL312
2.784
THR313
3.378
ARG314
2.235
HIS315
2.554
SER326
4.572
THR327
3.576
ASN328
2.931
ASP375
3.756
PDB ID: 4I3L      Crystal structure of a metabolic reductase with 6-benzyl-1-hydroxy-4-methylpyridin-2(1H)-one
Method X-ray diffraction Resolution 3.29 Å Mutation Yes [5]
PDB Sequence
KISGGSVVEM
13
QGDEMTRIIW
23
ELIKEKLIFP
33
YVELDLHSYD
43
LGIENRDATN
53

DQVTKDAAEA
63
IKKHNVGVKC
73
ATITPDEKRV
83
EEFKLKQMWK
93
SPNGTIRNIL
103

GGTVFREAII
113
CKNPIIIGHH
133
ATDFVVPGPG
150
KVEITYTPSD
160
GTQKVTYLVH
170

NFEEGGGVAM
180
GMYNQDKSIE
190
DFAHSSFQMA
200
LSKGWPLYLS
210
TKNTILKKYD
220

GRFKDIFQEI
230
YDKQYKSQFE
240
AQKIWYEHRL
250
IDDMVGFIWA
268
CKNLGMMTSV
294

LVCPDGKTVE
304
AEAAHGTVTR
314
HYRMYQKGQE
324
TSTNPIASIF
334
AWTRGLAHRA
344

KLDNNKELAF
354
FANALEEVSI
364
ETIEAGFMTK
374
DLAACIKGLP
384
NVQRSDYLNT
394

FEFMDKLGEN
404
LKIKLAQ
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .NDP or .NDP2 or .NDP3 or :3NDP;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
4.700
LYS72
2.951
CYS73
4.745
ALA74
3.381
THR75
2.580
ILE76
3.762
THR77
2.679
ARG82
3.369
ASN96
3.753
LEU288
3.558
GLY289
3.718
GLU306
3.384
ALA307
4.334
Residue
Distance (Å)
ALA308
4.007
HIS309
3.415
GLY310
2.797
THR311
2.918
VAL312
3.091
THR313
2.976
ARG314
2.409
HIS315
2.949
SER326
4.326
THR327
3.509
ASN328
2.848
ASP375
4.056
PDB ID: 4I3K      Crystal structure of a metabolic reductase with 1-hydroxy-6-(4-hydroxybenzyl)-4-methylpyridin-2(1H)-one
Method X-ray diffraction Resolution 3.31 Å Mutation Yes [5]
PDB Sequence
KISGGSVVEM
13
QGDEMTRIIW
23
ELIKEKLIFP
33
YVELDLHSYD
43
LGIENRDATN
53

DQVTKDAAEA
63
IKKHNVGVKC
73
ATITPDEKRV
83
EEFKLKQMWK
93
SPNGTIRNIL
103

GGTVFREAII
113
CKNPIIIGHH
133
ATDFVVPGPG
150
KVEITYTPSD
160
GTQKVTYLVH
170

NFEEGGGVAM
180
GMYNQDKSIE
190
DFAHSSFQMA
200
LSKGWPLYLS
210
TKNTILKKYD
220

GRFKDIFQEI
230
YDKQYKSQFE
240
AQKIWYEHRL
250
IDDMVGFIWA
268
CKNLGMMTSV
294

LVCPDGKTVE
304
AEAAHGTVTR
314
HYRMYQKGQE
324
TSTNPIASIF
334
AWTRGLAHRA
344

KLDNNKELAF
354
FANALEEVSI
364
ETIEAGFMTK
374
DLAACIKGLP
384
NVQRSDYLNT
394

FEFMDKLGEN
404
LKIKLAQ
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .NDP or .NDP2 or .NDP3 or :3NDP;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:79 or .A:82 or .A:94 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; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
GLU17
4.858
LYS72
2.964
CYS73
4.464
ALA74
3.332
THR75
2.406
ILE76
4.020
THR77
2.970
ASP79
4.999
ARG82
3.171
SER94
4.961
PRO95
4.043
ASN96
2.933
LEU288
4.165
GLY289
3.823
Residue
Distance (Å)
GLU306
3.247
ALA308
4.737
HIS309
3.477
GLY310
2.830
THR311
2.753
VAL312
3.319
THR313
3.049
ARG314
2.555
HIS315
2.491
SER326
4.456
THR327
3.300
ASN328
2.996
ASP375
4.011
PDB ID: 5TQH      IDH1 R132H mutant in complex with IDH889
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
HAQYRATDFV
145
VPGPGKVEIT
155

YTPSDGTQKV
165
TYLVHNFEEG
175
GGVAMGMYNQ
185
DKSIEDFAHS
195
SFQMALSKGW
205

PLYLSTKNTI
215
LKKYDGRFKD
225
IFQEIYDKQY
235
KSQFEAQKIW
245
YEHRLIDDMV
255

AQAMKSEGGF
265
IWACKNSDSV
281
AQGYGSLGMM
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

A
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .NDP or .NDP2 or .NDP3 or :3NDP;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:283 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
4.691
LYS72
3.433
CYS73
4.718
ALA74
3.469
THR75
3.039
ILE76
3.711
THR77
3.027
ARG82
3.104
ASN96
3.472
GLN283
3.662
LEU288
3.398
GLY289
3.770
GLU306
3.573
Residue
Distance (Å)
ALA307
4.695
ALA308
4.368
HIS309
3.381
GLY310
2.909
THR311
3.004
VAL312
2.782
THR313
3.297
ARG314
2.768
HIS315
2.707
SER326
4.486
THR327
3.673
ASN328
2.822
ASP375
4.151
PDB ID: 6B0Z      IDH1 R132H mutant in complex with IDH305
Method X-ray diffraction Resolution 2.33 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
HAATDFVVPG
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
CKNQSDSVAQ
283
GYGSLGMMTS
293
VLVCPDGKTV
303
EAEAAHGTVT
313

RHYRMYQKGQ
323
ETSTNPIASI
333
FAWTRGLAHR
343
AKLDNNKELA
353
FFANALEEVS
363

IETIEAGFMT
373
KDLAACIKGL
383
PNVQRSDYLN
393
TFEFMDKLGE
403
NLKIKLAQA
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .NDP or .NDP2 or .NDP3 or :3NDP;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:283 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
4.661
LYS72
3.602
CYS73
4.866
ALA74
3.607
THR75
3.043
ILE76
3.860
THR77
2.953
ARG82
3.239
ASN96
3.271
GLN283
3.967
LEU288
3.654
GLY289
3.821
GLU306
3.923
Residue
Distance (Å)
ALA307
4.652
ALA308
4.489
HIS309
3.313
GLY310
2.846
THR311
3.049
VAL312
2.753
THR313
3.348
ARG314
2.509
HIS315
2.745
SER326
4.561
THR327
3.624
ASN328
2.799
ASP375
4.078
PDB ID: 5SVF      IDH1 R132H in complex with IDH125
Method X-ray diffraction Resolution 2.34 Å Mutation Yes [8]
PDB Sequence
KISGGSVVEM
13
QGDEMTRIIW
23
ELIKEKLIFP
33
YVELDLHSYD
43
LGIENRDATN
53

DQVTKDAAEA
63
IKKHNVGVKC
73
ATITPDEKRV
83
EEFKLKQMWK
93
SPNGTIRNIL
103

GGTVFREAII
113
CKNIPRLVSG
123
WVKPIIIGHH
133
AATDFVVPGP
149
GKVEITYTPS
159

DGTQKVTYLV
169
HNFEEGGGVA
179
MGMYNQDKSI
189
EDFAHSSFQM
199
ALSKGWPLYL
209

STKNTILKKY
219
DGRFKDIFQE
229
IYDKQYKSQF
239
EAQKIWYEHR
249
LIDDMVAQAM
259

KSEGGFIWAC
269
KNQSDSVAQG
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
LKIKLAQA
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .NDP or .NDP2 or .NDP3 or :3NDP;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:283 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
4.720
LYS72
3.634
CYS73
4.863
ALA74
3.593
THR75
3.001
ILE76
3.810
THR77
3.029
ARG82
3.043
ASN96
3.228
GLN283
3.796
LEU288
3.634
GLY289
3.809
GLU306
3.382
Residue
Distance (Å)
ALA307
4.618
ALA308
4.535
HIS309
3.285
GLY310
2.906
THR311
2.988
VAL312
2.671
THR313
3.285
ARG314
2.533
HIS315
2.934
SER326
4.547
THR327
3.627
ASN328
2.859
ASP375
4.116
PDB ID: 5SUN      IDH1 R132H in complex with IDH146
Method X-ray diffraction Resolution 2.48 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
ATDFVVPGPG
150
KVEITYTPSD
160

GTQKVTYLVH
170
NFEEGGGVAM
180
GMYNQDKSIE
190
DFAHSSFQMA
200
LSKGWPLYLS
210

TKNTILKKYD
220
GRFKDIFQEI
230
YDKQYKSQFE
240
AQKIWYEHRL
250
IDDMVAQAMK
260

SEGGFIWACK
270
NSLGMMTSVL
295
VCPDGKTVEA
305
EAAHGTVTRH
315
YRMYQKGQET
325

STNPIASIFA
335
WTRGLAHRAK
345
LDNNKELAFF
355
ANALEEVSIE
365
TIEAGFMTKD
375

LAACIKGLPN
385
VQRSDYLNTF
395
EFMDKLGENL
405
KIKLAQAK
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .NDP or .NDP2 or .NDP3 or :3NDP;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
4.553
LYS72
3.475
CYS73
4.949
ALA74
3.739
THR75
2.981
ILE76
3.589
THR77
2.891
ARG82
3.067
ASN96
3.394
LEU288
3.796
GLY289
3.882
GLU306
3.578
ALA307
4.369
Residue
Distance (Å)
ALA308
4.622
HIS309
3.271
GLY310
2.458
THR311
3.024
VAL312
2.748
THR313
3.256
ARG314
2.388
HIS315
2.833
SER326
4.515
THR327
3.613
ASN328
2.910
ASP375
3.978
PDB ID: 5K10      Cryo-EM structure of isocitrate dehydrogenase (IDH1)
Method Electron microscopy Resolution 3.80 Å Mutation No [9]
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
GWVKPIIIGC
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
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .NDP or .NDP2 or .NDP3 or :3NDP;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:81 or .A:82 or .A:96 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:327 or .A:328 or .A:329 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
3.947
LYS72
3.635
ALA74
3.823
THR75
3.214
ILE76
3.115
THR77
2.477
LYS81
4.966
ARG82
2.565
ASN96
3.678
SER287
4.278
LEU288
3.222
GLY289
4.274
GLU306
3.896
Residue
Distance (Å)
ALA307
4.269
ALA308
4.839
HIS309
3.051
GLY310
3.126
THR311
2.613
VAL312
3.127
THR313
2.515
ARG314
2.012
HIS315
3.606
THR327
2.546
ASN328
2.949
PRO329
4.604
ASP375
3.012
PDB ID: 5K11      Cryo-EM structure of isocitrate dehydrogenase (IDH1) in inhibitor-bound state
Method Electron microscopy Resolution 3.80 Å Mutation No [9]
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
GWVKPIIIGC
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
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .NDP or .NDP2 or .NDP3 or :3NDP;style chemicals stick;color identity;select .A:72 or .A:74 or .A:75 or .A:76 or .A:77 or .A:82 or .A:94 or .A:95 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)
LYS72
3.984
ALA74
4.039
THR75
3.255
ILE76
2.638
THR77
2.724
ARG82
3.440
SER94
4.658
PRO95
4.994
ASN96
2.787
LEU288
2.812
GLY289
3.651
GLU306
3.361
ALA307
3.972
Residue
Distance (Å)
ALA308
4.057
HIS309
3.292
GLY310
2.769
THR311
3.187
VAL312
3.392
THR313
3.026
ARG314
3.248
HIS315
2.485
SER326
3.821
THR327
4.055
ASN328
3.271
ASP375
3.164
PDB ID: 7PJM      Crystal Structure of Ivosidenib-resistant IDH1 variant R132C S280F in complex with NADPH and Ca2+/2-Oxoglutarate
Method X-ray diffraction Resolution 2.10 Å Mutation Yes [10]
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
GWVKPIIIGC
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
DGDVQSDFVA
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
KLLEH
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .NDP or .NDP2 or .NDP3 or :3NDP;style chemicals stick;color identity;select .A:17 or .A:19 or .A:22 or .A:72 or .A:73 or .A:74 or .A:75 or .A:76 or .A:77 or .A:82 or .A:95 or .A:96 or .A:100 or .A:283 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:329 or .A:330 or .A:331 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
3.551
THR19
4.871
ILE22
4.610
LYS72
2.257
CYS73
4.101
ALA74
2.545
THR75
1.804
ILE76
2.050
THR77
2.371
ARG82
2.337
PRO95
4.978
ASN96
2.029
ARG100
4.354
GLN283
4.862
SER287
4.625
LEU288
2.520
GLY289
3.164
Residue
Distance (Å)
GLU306
4.568
ALA307
3.333
ALA308
2.231
HIS309
2.469
GLY310
1.953
THR311
2.139
VAL312
1.840
THR313
2.782
ARG314
1.705
HIS315
2.080
SER326
3.816
THR327
2.949
ASN328
1.856
PRO329
4.046
ILE330
4.915
ALA331
4.449
ASP375
3.030
PDB ID: 8BAY      Crystal Structure of IDH1 variant R132C S280F in complex with NADPH, Ca2+ and 3-butyl-2-oxoglutarate
Method X-ray diffraction Resolution 2.35 Å Mutation Yes [11]
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
GWVKPIIIGC
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
DGDVQSDFVA
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
KLLE
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .NDP or .NDP2 or .NDP3 or :3NDP;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: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
4.819
LYS72
4.465
ALA74
4.210
THR75
3.192
ILE76
3.278
THR77
3.074
ARG82
3.126
ASN96
3.554
ALA307
4.251
ALA308
2.997
HIS309
3.278
Residue
Distance (Å)
GLY310
3.208
THR311
3.123
VAL312
2.997
THR313
3.272
ARG314
3.464
HIS315
2.583
SER326
3.652
THR327
3.672
ASN328
2.777
ASP375
3.900
PDB ID: 7PJN      Crystal Structure of Ivosidenib-resistant IDH1 variant R132C S280F in complex with NADPH and inhibitor DS-1001B
Method X-ray diffraction Resolution 2.45 Å Mutation Yes [10]
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
GWVKPIIIGC
132
HAYRATDFVV
146
PGPGKVEITY
156

TPSDGTQKVT
166
YLVHNFEEGG
176
GVAMGMYNQD
186
KSIEDFAHSS
196
FQMALSKGWP
206

LYLSTKNTIL
216
KKYDGRFKDI
226
FQEIYDKQYK
236
SQFEAQKIWY
246
EHRLIDDMVA
256

QAMKSEGGFI
266
WACKNYDGDV
276
QSDFVAQGYG
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

IKLAQA
> Chain B
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
CHARATDFVV
146
PGPGKVEITY
156

TPSDGTQKVT
166
YLVHNFEEGG
176
GVAMGMYNQD
186
KSIEDFAHSS
196
FQMALSKGWP
206

LYLSTKNTIL
216
KKYDGRFKDI
226
FQEIYDKQYK
236
SQFEAQKIWY
246
EHRLIDDMVA
256

QAMKSEGGFI
266
WACKNYDGDV
276
QSDFVAQGYG
286
SLGMMTSVLV
296
CPDGKTVEAE
306

AAHGTVTRHY
316
RMYQKGQETS
326
TNPIASIFAW
336
TRGLAHRAKL
346
DNNKELAFFA
356

NALEEVSIET
366
IEAGFMTKDL
376
AAIKGLPNVQ
387
RSDYLNTFEF
397
MDKLGENLKI
407

KLAQ
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .NDP or .NDP2 or .NDP3 or :3NDP;style chemicals stick;color identity;select .A:17 or .A:19 or .A:22 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:109 or .A:283 or .A:286 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:330 or .A:331 or .A:375 or .B:17 or .B:19 or .B:22 or .B:72 or .B:73 or .B:74 or .B:75 or .B:76 or .B:77 or .B:82 or .B:96 or .B:100 or .B:283 or .B:286 or .B:288 or .B:289 or .B:306 or .B:307 or .B:308 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:331 or .B:373 or .B:375 or .B:383; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue [Chain]
Distance (Å)
GLU17[A]
3.712
THR19[A]
4.987
ILE22[A]
4.343
LYS72[A]
2.827
CYS73[A]
4.525
ALA74[A]
2.559
THR75[A]
2.090
ILE76[A]
2.837
THR77[A]
2.424
ARG82[A]
2.124
ASN96[A]
2.456
ARG100[A]
4.652
ARG109[A]
4.946
GLN283[A]
3.009
GLY286[A]
4.837
LEU288[A]
2.374
GLY289[A]
3.048
GLU306[A]
3.095
ALA307[A]
4.143
ALA308[A]
3.335
HIS309[A]
2.419
GLY310[A]
2.008
THR311[A]
2.159
VAL312[A]
1.616
THR313[A]
2.387
ARG314[A]
1.819
HIS315[A]
1.995
SER326[A]
3.757
THR327[A]
2.623
ASN328[A]
1.889
PRO329[A]
4.019
ILE330[A]
4.995
ALA331[A]
4.533
ASP375[A]
2.802
Residue [Chain]
Distance (Å)
GLU17[B]
3.406
THR19[B]
4.665
ILE22[B]
4.606
LYS72[B]
2.845
CYS73[B]
4.700
ALA74[B]
2.703
THR75[B]
2.034
ILE76[B]
2.688
THR77[B]
2.362
ARG82[B]
2.112
ASN96[B]
2.208
ARG100[B]
4.058
GLN283[B]
2.877
GLY286[B]
4.591
LEU288[B]
2.854
GLY289[B]
3.085
GLU306[B]
3.016
ALA307[B]
4.117
ALA308[B]
3.354
HIS309[B]
2.505
GLY310[B]
2.066
THR311[B]
2.160
VAL312[B]
1.868
THR313[B]
2.448
ARG314[B]
2.249
HIS315[B]
1.873
SER326[B]
3.838
THR327[B]
2.626
ASN328[B]
1.876
PRO329[B]
4.022
ALA331[B]
4.597
THR373[B]
4.909
ASP375[B]
2.827
LEU383[B]
4.482
PDB ID: 3INM      Crystal structure of human cytosolic NADP(+)-dependent isocitrate dehydrogenase R132H mutant in complex with NADPH, ALPHA-KETOGLUTARATE and CALCIUM(2+)
Method X-ray diffraction Resolution 2.10 Å Mutation Yes [12]
PDB Sequence
KISGGSVVEM
13
QGDEMTRIIW
23
ELIKEKLIFP
33
YVELDLHSYD
43
LGIENRDATN
53

DQVTKDAAEA
63
IKKHNVGVKC
73
ATITPDEKRV
83
EEFKLKQMWK
93
SPNGTIRNIL
103

GGTVFREAII
113
CKNIPRLVSG
123
WVKPIIIGHH
133
AYGDQYRATD
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
GFIWACKNYD
273
GDVQSDSVAQ
283
GYGSLGMMTS
293
VLVCPDGKTV
303

EAEAAHGTVT
313
RHYRMYQKGQ
323
ETSTNPIASI
333
FAWTRGLAHR
343
AKLDNNKELA
353

FFANALEEVS
363
IETIEAGFMT
373
KDLAACIKGL
383
PNVQRSDYLN
393
TFEFMDKLGE
403

NLKIKLA
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .NDP or .NDP2 or .NDP3 or :3NDP;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: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
4.670
LYS72
3.699
CYS73
4.792
ALA74
3.546
THR75
2.840
ILE76
3.744
THR77
3.371
ARG82
3.026
ASN96
2.870
SER287
4.751
LEU288
3.515
GLY289
4.211
GLU306
4.684
Residue
Distance (Å)
ALA307
3.928
ALA308
3.764
HIS309
3.560
GLY310
2.928
THR311
3.136
VAL312
2.627
THR313
3.108
ARG314
3.608
HIS315
2.743
SER326
4.766
THR327
3.392
ASN328
2.975
ASP375
4.095
PDB ID: 6VEI      Crystal Structure of Human Cytosolic Isocitrate Dehydrogenase (IDH1) R132H Mutant in Complex with NADPH and AG-881 (Vorasidenib) Inhibitor
Method X-ray diffraction Resolution 2.10 Å Mutation Yes [13]
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
KLS
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .NDP or .NDP2 or .NDP3 or :3NDP;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: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
4.632
LYS72
3.555
CYS73
4.922
ALA74
3.682
THR75
2.998
ILE76
3.773
THR77
3.125
ARG82
3.138
ASN96
2.922
SER287
4.608
LEU288
3.642
GLY289
3.631
GLU306
3.240
Residue
Distance (Å)
ALA307
3.720
ALA308
4.604
HIS309
3.201
GLY310
2.792
THR311
2.991
VAL312
2.720
THR313
3.260
ARG314
2.345
HIS315
2.807
SER326
4.457
THR327
3.606
ASN328
2.820
ASP375
3.982
PDB ID: 6VG0      CRYSTAL STRUCTURE OF HUMAN CYTOSOLIC ISOCITRATE DEHYDROGENASE (IDH1) R132H MUTANT IN COMPLEX WITH NADPH and AGI-15056
Method X-ray diffraction Resolution 2.66 Å Mutation Yes [13]
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
HHAYGDQYRA
141
TDFVVPGPGK
151

VEITYTPSDG
161
TQKVTYLVHN
171
FEEGGGVAMG
181
MYNQDKSIED
191
FAHSSFQMAL
201

SKGWPLYLST
211
KNTILKKYDG
221
RFKDIFQEIY
231
DKQYKSQFEA
241
QKIWYEHRLI
251

DDMVAQAMKS
261
EGGFIWACKN
271
YDGDVQSDSV
281
AQGYGSLGMM
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 .NDP or .NDP2 or .NDP3 or :3NDP;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: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
4.925
LYS72
3.607
CYS73
4.729
ALA74
3.680
THR75
3.062
ILE76
3.905
THR77
3.323
ARG82
3.279
ASN96
3.229
SER287
4.858
LEU288
3.819
GLY289
3.755
GLU306
3.204
Residue
Distance (Å)
ALA307
3.668
ALA308
4.293
HIS309
3.371
GLY310
2.631
THR311
2.932
VAL312
2.700
THR313
3.196
ARG314
2.747
HIS315
2.763
SER326
4.412
THR327
3.545
ASN328
2.860
ASP375
4.089
PDB ID: 6ADG      Crystal Structures of IDH1 R132H in complex with AG-881
Method X-ray diffraction Resolution 3.00 Å Mutation Yes [14]
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 .NDP or .NDP2 or .NDP3 or :3NDP;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: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:329 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
4.690
LYS72
3.929
ALA74
3.827
THR75
3.329
ILE76
3.727
THR77
3.178
ARG82
3.161
ASN96
2.900
SER287
4.747
LEU288
3.863
GLY289
3.769
GLU306
3.691
ALA307
3.367
Residue
Distance (Å)
ALA308
3.894
HIS309
3.305
GLY310
2.334
THR311
2.806
VAL312
2.679
THR313
3.260
ARG314
2.282
HIS315
2.721
SER326
4.380
THR327
3.486
ASN328
2.833
PRO329
4.979
ASP375
4.080
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 A Potent Blood-Brain Barrier-Permeable Mutant IDH1 Inhibitor Suppresses the Growth of Glioblastoma with IDH1 Mutation in a Patient-Derived Orthotopic Xenograft Model. Mol Cancer Ther. 2020 Feb;19(2):375-383.
REF 3 Discovery and Optimization of Allosteric Inhibitors of Mutant Isocitrate Dehydrogenase 1 (R132H IDH1) Displaying Activity in Human Acute Myeloid Leukemia Cells. J Med Chem. 2016 Dec 22;59(24):11120-11137.
REF 4 Inhibition of Cancer-Associated Mutant Isocitrate Dehydrogenases by 2-Thiohydantoin Compounds. J Med Chem. 2015 Sep 10;58(17):6899-6908.
REF 5 Crystallographic Investigation and Selective Inhibition of Mutant Isocitrate Dehydrogenase. ACS Med Chem Lett. 2013 Jun 13;4(6):542-546.
REF 6 Optimization of 3-Pyrimidin-4-yl-oxazolidin-2-ones as Allosteric and Mutant Specific Inhibitors of IDH1. ACS Med Chem Lett. 2016 Dec 16;8(2):151-156.
REF 7 Discovery and Evaluation of Clinical Candidate IDH305, a Brain Penetrant Mutant IDH1 Inhibitor. ACS Med Chem Lett. 2017 Sep 18;8(10):1116-1121.
REF 8 Allosteric Mutant IDH1 Inhibitors Reveal Mechanisms for IDH1 Mutant and Isoform Selectivity. Structure. 2017 Mar 7;25(3):506-513.
REF 9 Breaking Cryo-EM Resolution Barriers to Facilitate Drug Discovery. Cell. 2016 Jun 16;165(7):1698-1707.
REF 10 Resistance to the isocitrate dehydrogenase 1 mutant inhibitor ivosidenib can be overcome by alternative dimer-interface binding inhibitors. Nat Commun. 2022 Aug 15;13(1):4785.
REF 11 Natural and synthetic 2-oxoglutarate derivatives are substrates for oncogenic variants of human isocitrate dehydrogenase 1 and 2. J Biol Chem. 2023 Feb;299(2):102873.
REF 12 Cancer-associated IDH1 mutations produce 2-hydroxyglutarate. Nature. 2009 Dec 10;462(7274):739-44.
REF 13 Vorasidenib (AG-881): A First-in-Class, Brain-Penetrant Dual Inhibitor of Mutant IDH1 and 2 for Treatment of Glioma. ACS Med Chem Lett. 2020 Jan 22;11(2):101-107.
REF 14 Crystal structures of pan-IDH inhibitor AG-881 in complex with mutant human IDH1 and IDH2. Biochem Biophys Res Commun. 2018 Sep 18;503(4):2912-2917.

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