Target Binding Site Detail
| Target General Information | Top | ||||
|---|---|---|---|---|---|
| Target ID | T86591 | Target Info | |||
| Target Name | Peroxisome proliferator-activated receptor alpha (PPARA) | ||||
| Synonyms | Peroxisome proliferater-activated receptor alpha; PPARalpha; PPAR-alpha; PPAR; Nuclear receptor subfamily 1 group C member 1; NR1C1 | ||||
| Target Type | Successful Target | ||||
| Gene Name | PPARA | ||||
| Biochemical Class | Nuclear hormone receptor | ||||
| UniProt ID | |||||
| Ligand General Information | Top | ||||
|---|---|---|---|---|---|
| Ligand Name | Pemafibrate | Ligand Info | |||
| Canonical SMILES | CCC(C(=O)O)OC1=CC=CC(=C1)CN(CCCOC2=CC=C(C=C2)OC)C3=NC4=CC=CC=C4O3 | ||||
| InChI | 1S/C28H30N2O6/c1-3-25(27(31)32)35-23-9-6-8-20(18-23)19-30(28-29-24-10-4-5-11-26(24)36-28)16-7-17-34-22-14-12-21(33-2)13-15-22/h4-6,8-15,18,25H,3,7,16-17,19H2,1-2H3,(H,31,32)/t25-/m1/s1 | ||||
| InChIKey | ZHKNLJLMDFQVHJ-RUZDIDTESA-N | ||||
| PubChem Compound ID | 11526038 | ||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| PDB ID: 6L96 Structure of PPARalpha-LBD/pemafibrate/SRC1 peptide | ||||||
| Method | X-ray diffraction | Resolution | 3.20 Å | Mutation | No | [1] |
| PDB Sequence |
DLKSLAKRIY
212 EAYLKNFNMN222 KVKARVILSG232 KASNNPPFVI242 HDMETLCMAE252 KTLVEAEVRI 272 FHCCQCTSVE282 TVTELTEFAK292 AIPGFANLDL302 NDQVTLLKYG312 VYEAIFAMLS 322 SVMNKDGMLV332 AYGNGFITRE342 FLKSLRKPFC352 DIMEPKFDFA362 MKFNALELDD 372 SDISLFVAAI382 ICCGDRPGLL392 NVGHIEKMQE402 GIVHVLRLHL412 QSNHPDDIFL 422 FPKLLQKMAD432 LRQLVTEHAQ442 LVQIIKKTES452 DAALHPLLQE462 IYRDM |
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|
|
ILE242
4.365
LEU248
4.141
ALA251
4.521
GLU252
4.743
LEU255
4.714
VAL256
3.420
ILE272
3.955
PHE273
3.576
CYS275
3.367
CYS276
3.182
GLN277
3.703
THR279
3.162
SER280
2.399
THR283
4.533
TYR314
2.514
ILE317
3.537
|
|||||
| PDB ID: 6KB4 X-ray structure of human PPARalpha ligand binding domain-pemafibrate co-crystals obtained by delipidation and cross-seeding | ||||||
| Method | X-ray diffraction | Resolution | 1.42 Å | Mutation | No | [2] |
| PDB Sequence |
MTADLKSLAK
208 RIYEAYLKNF218 NMNKVKARVI228 LSGSNNPPFV240 IHDMETLCMA250 EKTLVAKLVA 260 NGIQNKEAEV270 RIFHCCQCTS280 VETVTELTEF290 AKAIPGFANL300 DLNDQVTLLK 310 YGVYEAIFAM320 LSSVMNKDGM330 LVAYGNGFIT340 REFLKSLRKP350 FCDIMEPKFD 360 FAMKFNALEL370 DDSDISLFVA380 AIICCGDRPG390 LLNVGHIEKM400 QEGIVHVLRL 410 HLQSNHPDDI420 FLFPKLLQKM430 ADLRQLVTEH440 AQLVQIIKKT450 ESDAALHPLL 460 QEIYRDMY
|
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|
|
MET220
3.259
ILE241
2.791
LEU247
3.962
ALA250
3.874
GLU251
3.640
LEU254
4.853
VAL255
4.161
ILE272
3.791
PHE273
2.680
CYS275
3.619
CYS276
2.687
GLN277
3.223
THR279
2.889
SER280
2.569
THR283
3.993
TYR314
2.736
ALA316
4.941
ILE317
3.151
|
|||||
| PDB ID: 6KAZ X-ray structure of human PPARalpha ligand binding domain-pemafibrate co-crystals obtained by soaking | ||||||
| Method | X-ray diffraction | Resolution | 1.48 Å | Mutation | No | [2] |
| PDB Sequence |
DLKSLAKRIY
211 EAYLKNFNMN221 KVKARVILSG231 PPFVIHDMET246 LCMAEKTLVA256 KLVANGIQNK 266 EAEVRIFHCC276 QCTSVETVTE286 LTEFAKAIPG296 FANLDLNDQV306 TLLKYGVYEA 316 IFAMLSSVMN326 KDGMLVAYGN336 GFITREFLKS346 LRKPFCDIME356 PKFDFAMKFN 366 ALELDDSDIS376 LFVAAIICCG386 DRPGLLNVGH396 IEKMQEGIVH406 VLRLHLQSNH 416 PDDIFLFPKL426 LQKMADLRQL436 VTEHAQLVQI446 IKKTESDAAL456 HPLLQEIYRD 466 MY
|
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|
|
MET220
3.337
ILE241
3.063
LEU247
3.929
ALA250
3.828
GLU251
3.338
VAL255
3.933
ILE272
3.735
PHE273
2.717
CYS275
3.598
CYS276
2.683
GLN277
3.335
THR279
2.943
SER280
2.579
THR283
3.899
TYR314
2.776
ALA316
4.994
ILE317
3.175
|
|||||
| PDB ID: 7BQ2 X-ray structure of human PPARalpha ligand binding domain-pemafibrate-SRC1 coactivator peptide co-crystals obtained by soaking | ||||||
| Method | X-ray diffraction | Resolution | 1.52 Å | Mutation | No | [2] |
| PDB Sequence |
ADLKSLAKRI
210 YEAYLKNFNM220 NKVKARVILS230 GPPFVIHDME245 TLCMAEKTLV255 AKLVANKEAE 269 VRIFHCCQCT279 SVETVTELTE289 FAKAIPGFAN299 LDLNDQVTLL309 KYGVYEAIFA 319 MLSSVMNKDG329 MLVAYGNGFI339 TREFLKSLRK349 PFCDIMEPKF359 DFAMKFNALE 369 LDDSDISLFV379 AAIICCGDRP389 GLLNVGHIEK399 MQEGIVHVLR409 LHLQSNHPDD 419 IFLFPKLLQK429 MADLRQLVTE439 HAQLVQIIKK449 TESDAALHPL459 LQEIYRDMY |
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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 .P7F or .P7F2 or .P7F3 or :3P7F;style chemicals stick;color identity;select .A:220 or .A:241 or .A:247 or .A:250 or .A:251 or .A:255 or .A:272 or .A:273 or .A:275 or .A:276 or .A:277 or .A:279 or .A:280 or .A:283 or .A:314 or .A:316 or .A:317 or .A:318 or .A:320 or .A:321 or .A:324 or .A:330 or .A:331 or .A:332 or .A:333 or .A:339 or .A:354 or .A:355 or .A:358 or .A:440 or .A:444 or .A:456 or .A:460 or .A:464; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
MET220
3.398
ILE241
3.009
LEU247
3.986
ALA250
3.824
GLU251
3.491
VAL255
3.942
ILE272
3.672
PHE273
2.598
CYS275
3.571
CYS276
2.832
GLN277
3.341
THR279
2.803
SER280
2.475
THR283
3.876
TYR314
2.631
ALA316
4.978
ILE317
3.093
|
|||||
| PDB ID: 6KB9 X-ray structure of human PPARalpha ligand binding domain-pemafibrate co-crystals obtained by cross-seeding | ||||||
| Method | X-ray diffraction | Resolution | 1.55 Å | Mutation | No | [2] |
| PDB Sequence |
MTADLKSLAK
208 RIYEAYLKNF218 NMNKVKARVI228 LSGSNNPPFV240 IHDMETLCMA250 EKTLVAKLVA 260 NGIQNKEAEV270 RIFHCCQCTS280 VETVTELTEF290 AKAIPGFANL300 DLNDQVTLLK 310 YGVYEAIFAM320 LSSVMNKDGM330 LVAYGNGFIT340 REFLKSLRKP350 FCDIMEPKFD 360 FAMKFNALEL370 DDSDISLFVA380 AIICCGDRPG390 LLNVGHIEKM400 QEGIVHVLRL 410 HLQSNHPDDI420 FLFPKLLQKM430 ADLRQLVTEH440 AQLVQIIKKT450 ESDAALHPLL 460 QEIYRDMY
|
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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 .P7F or .P7F2 or .P7F3 or :3P7F;style chemicals stick;color identity;select .A:220 or .A:241 or .A:247 or .A:250 or .A:251 or .A:254 or .A:255 or .A:272 or .A:273 or .A:275 or .A:276 or .A:277 or .A:279 or .A:280 or .A:283 or .A:314 or .A:316 or .A:317 or .A:318 or .A:320 or .A:321 or .A:324 or .A:330 or .A:331 or .A:332 or .A:333 or .A:339 or .A:354 or .A:355 or .A:358 or .A:440 or .A:444 or .A:456 or .A:460 or .A:464; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
MET220
3.290
ILE241
2.968
LEU247
4.067
ALA250
3.793
GLU251
3.530
LEU254
4.734
VAL255
3.978
ILE272
3.791
PHE273
2.669
CYS275
3.571
CYS276
2.765
GLN277
3.273
THR279
2.872
SER280
2.562
THR283
4.063
TYR314
2.721
ALA316
4.968
ILE317
3.140
|
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| References | Top | ||||
|---|---|---|---|---|---|
| REF 1 | Elucidation of Molecular Mechanism of a Selective PPARAlpha Modulator, Pemafibrate, through Combinational Approaches of X-ray Crystallography, Thermodynamic Analysis, and First-Principle Calculations. Int J Mol Sci. 2020 Jan 6;21(1):361. | ||||
| REF 2 | PPARAlpha Ligand-Binding Domain Structures with Endogenous Fatty Acids and Fibrates. iScience. 2020 Oct 23;23(11):101727. | ||||
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