Binding Site Information of Target
| Target General Information | Top | ||||
|---|---|---|---|---|---|
| Target ID | T32972 | Target Info | |||
| Target Name | Lanosterol 14-alpha demethylase (CYP51A1) | ||||
| Synonyms | Cytochrome P450LI; Cytochrome P45014DM; Cytochrome P450-14DM; Cytochrome P450 51A1 | ||||
| Target Type | Clinical trial Target | ||||
| Gene Name | CYP51A1 | ||||
| Biochemical Class | Cytochrome P450 family | ||||
| UniProt ID | |||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| Ligand Name: Ketoconazole | Ligand Info | |||||
| Structure Description | Crystal structure of human lanosterol 14alpha-demethylase (CYP51) in complex with ketoconazole | PDB:3LD6 | ||||
| Method | X-ray diffraction | Resolution | 2.80 Å | Mutation | No | [1] |
| PDB Sequence |
VKSPPYIFSP
67 IPFLGHAIAF77 GKSPIEFLEN87 AYEKYGPVFS97 FTMVGKTFTY107 LLGSDAAALL 117 FNSKNEDLNA127 EDVYSRLTTP137 VFGKGVAYDV147 PNPVFLEQKK157 MLKSGLNIAH 167 FKQHVSIIEK177 ETKEYFESWG187 ESGEKNVFEA197 LSELIILTAS207 HCLHGKEIRS 217 QLNEKVAQLY227 ADLDGGFSHA237 AWLLPGWLPL247 PSFRRRDRAH257 REIKDIFYKA 267 IQKRRQSQEK277 IDDILQTLLD287 ATYKDGRPLT297 DDEVAGMLIG307 LLLAGQHTSS 317 TTSAWMGFFL327 ARDKTLQKKC337 YLEQKTVCGE347 NLPPLTYDQL357 KDLNLLDRCI 367 KETLRLRPPI377 MIMMRMARTP387 QTVAGYTIPP397 GHQVCVSPTV407 NQRLKDSWVE 417 RLDFNPDRYL427 QDNPASGEKF437 AYVPFGAGRH447 RCIGENFAYV457 QIKTIWSTML 467 RLYEFDLIDG477 YFPTVNYTTM487 IHTPENPVIR497 YKRRS
|
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PHE77
3.869
PHE105
4.011
TYR107
4.544
TYR131
3.240
LEU134
3.757
THR135
4.338
PHE139
3.424
TYR145
3.494
PHE152
4.639
PHE234
3.669
HIS236
4.319
TRP239
3.564
|
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| Ligand Name: ATX-101 | Ligand Info | |||||
| Structure Description | Human sterol 14a-demethylase (CYP51) in complex with the functionally irreversible inhibitor (R)-N-(1-(3-chloro-4'-fluoro-[1,1'-biphenyl]-4-yl)-2-(1H-imidazol-1-yl)ethyl)-4-(5-(3-fluoro-5-(5-fluoropyrimidin-4-yl)phenyl)-1,3,4-oxadiazol-2-yl)benzamide | PDB:6Q2T | ||||
| Method | X-ray diffraction | Resolution | 2.80 Å | Mutation | No | [2] |
| PDB Sequence |
GKLPPYIFSP
67 IPFLGHAIAF77 GKSPIEFLEN87 AYEKYGPVFS97 FTMVGKTFTY107 LLGSDAAALL 117 FNSKNEDLNA127 EDVYSRLTTP137 VFGKGVAYDV147 PNPVFLEQKK157 MLKSGLNIAH 167 FKQHVSIIEK177 ETKEYFESWG187 ESGEKNVFEA197 LSELIILTAS207 HCLHGKEIRS 217 QLNEKVAQLY227 ADLDGGFSHA237 AWLLPGWLPL247 PSFRRRDRAH257 REIKDIFYKA 267 IQKRRQSQEK277 IDDILQTLLD287 ATYKDGRPLT297 DDEVAGMLIG307 LLLAGQHTSS 317 TTSAWMGFFL327 ARDKTLQKKC337 YLEQKTVCGE347 NLPPLTYDQL357 KDLNLLDRCI 367 KETLRLRPPI377 MIMMRMARTP387 QTVAGYTIPP397 GHQVCVSPTV407 NQRLKDSWVE 417 RLDFNPDRYL427 QDNPASGEKF437 AYVPFGAGRH447 RCIGENFAYV457 QIKTIWSTML 467 RLYEFDLIDG477 YFPTVNYTTM487 IHTPENPVIR497 YKRRS
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| Ligand Name: Lanosterol | Ligand Info | |||||
| Structure Description | Human sterol 14a-demethylase (CYP51) in complex with the substrate lanosterol | PDB:6UEZ | ||||
| Method | X-ray diffraction | Resolution | 1.98 Å | Mutation | Yes | [3] |
| PDB Sequence |
KGKLPPYIFS
66 PIPFLGHAIA76 FGKSPIEFLE86 NAYEKYGPVF96 SFTMVGKTFT106 YLLGSDAAAL 116 LFNSKNEDLN126 AEDVYSRLTT136 PVFGKGVAYD146 VPNPVFLEQK156 KMLKSGLNIA 166 HFKQHVSIIE176 KETKEYFESW186 GESGEKNVFE196 ALSELIILTA206 SHCLHGKEIR 216 SQLNEKVAQL226 YADLAGGFSH236 AAWLLPGWLP246 LPSFRRRDRA256 HREIKDIFYK 266 AIQKRRQSQE276 KIDDILQTLL286 DATYKDGRPL296 TDDEVAGMLI306 GLLLAGQATS 316 STTSAWMGFF326 LARDKTLQKK336 CYLEQKTVCG346 ENLPPLTYDQ356 LKDLNLLDRC 366 IKETLRLRPP376 IMIMMRMART386 PQTVAGYTIP396 PGHQVCVSPT406 VNQRLKDSWV 416 ERLDFNPDRY426 LQDNPASGEK436 FAYVPFGAGR446 HRCIGENFAY456 VQIKTIWSTM 466 LRLYEFDLID476 GYFPTVNYTT486 MIHTPENPVI496 RYKRRS
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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 .LAN or .LAN2 or .LAN3 or :3LAN;style chemicals stick;color identity;select .A:131 or .A:134 or .A:135 or .A:139 or .A:143 or .A:144 or .A:145 or .A:152 or .A:155 or .A:159 or .A:234 or .A:303 or .A:304 or .A:307 or .A:308 or .A:310 or .A:311 or .A:315 or .A:377 or .A:379 or .A:380 or .A:381 or .A:487 or .A:488; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
TYR131
3.482
LEU134
4.268
THR135
3.843
PHE139
3.696
VAL143
3.706
ALA144
4.075
TYR145
3.547
PHE152
3.699
GLN155
4.401
LEU159
3.408
PHE234
3.722
GLY303
3.483
|
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| Ligand Name: 1-[(2r)-2-[(4-Chlorobenzyl)oxy]-2-(2,4-Dichlorophenyl)ethyl]-1h-Imidazole | Ligand Info | |||||
| Structure Description | Crystal structure of human lanosterol 14alpha-demethylase (CYP51) in complex with econazole | PDB:3JUS | ||||
| Method | X-ray diffraction | Resolution | 2.90 Å | Mutation | No | [1] |
| PDB Sequence |
VKSPPYIFSP
67 IPFLGHAIAF77 GKSPIEFLEN87 AYEKYGPVFS97 FTMVGKTFTY107 LLGSDAAALL 117 FNSKNEDLNA127 EDVYSRLTTP137 VFGKGVAYDV147 PNPVFLEQKK157 MLKSGLNIAH 167 FKQHVSIIEK177 ETKEYFESWG187 ESGEKNVFEA197 LSELIILTAS207 HCLHGKEIRS 217 QLNEKVAQLY227 ADLDGGFSHA237 AWLLPGWLPL247 PSFRRRDRAH257 REIKDIFYKA 267 IQKRRQSQEK277 IDDILQTLLD287 ATYKDGRPLT297 DDEVAGMLIG307 LLLAGQHTSS 317 TTSAWMGFFL327 ARDKTLQKKC337 YLEQKTVCGE347 NLPPLTYDQL357 KDLNLLDRCI 367 KETLRLRPPI377 MIMMRMARTP387 QTVAGYTIPP397 GHQVCVSPTV407 NQRLKDSWVE 417 RLDFNPDRYL427 QDNPASGEKF437 AYVPFGAGRH447 RCIGENFAYV457 QIKTIWSTML 467 RLYEFDLIDG477 YFPTVNYTTM487 IHTPENPVIR497 YKRRS
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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 .ECL or .ECL2 or .ECL3 or :3ECL;style chemicals stick;color identity;select .A:131 or .A:134 or .A:135 or .A:139 or .A:144 or .A:145 or .A:152 or .A:159 or .A:234 or .A:304 or .A:307 or .A:308 or .A:311 or .A:312 or .A:315 or .A:377 or .A:379 or .A:449; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
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| Ligand Name: 1-[(2s)-2-[(4-Chlorobenzyl)oxy]-2-(2,4-Dichlorophenyl)ethyl]-1h-Imidazole | Ligand Info | |||||
| Structure Description | Crystal structure of human lanosterol 14alpha-demethylase (CYP51) in complex with econazole | PDB:3JUS | ||||
| Method | X-ray diffraction | Resolution | 2.90 Å | Mutation | No | [1] |
| PDB Sequence |
VKSPPYIFSP
67 IPFLGHAIAF77 GKSPIEFLEN87 AYEKYGPVFS97 FTMVGKTFTY107 LLGSDAAALL 117 FNSKNEDLNA127 EDVYSRLTTP137 VFGKGVAYDV147 PNPVFLEQKK157 MLKSGLNIAH 167 FKQHVSIIEK177 ETKEYFESWG187 ESGEKNVFEA197 LSELIILTAS207 HCLHGKEIRS 217 QLNEKVAQLY227 ADLDGGFSHA237 AWLLPGWLPL247 PSFRRRDRAH257 REIKDIFYKA 267 IQKRRQSQEK277 IDDILQTLLD287 ATYKDGRPLT297 DDEVAGMLIG307 LLLAGQHTSS 317 TTSAWMGFFL327 ARDKTLQKKC337 YLEQKTVCGE347 NLPPLTYDQL357 KDLNLLDRCI 367 KETLRLRPPI377 MIMMRMARTP387 QTVAGYTIPP397 GHQVCVSPTV407 NQRLKDSWVE 417 RLDFNPDRYL427 QDNPASGEKF437 AYVPFGAGRH447 RCIGENFAYV457 QIKTIWSTML 467 RLYEFDLIDG477 YFPTVNYTTM487 IHTPENPVIR497 YKRRS
|
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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 .ECN or .ECN2 or .ECN3 or :3ECN;style chemicals stick;color identity;select .A:130 or .A:131 or .A:134 or .A:135 or .A:139 or .A:144 or .A:145 or .A:152 or .A:159 or .A:234 or .A:304 or .A:307 or .A:308 or .A:311 or .A:315 or .A:377 or .A:449; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
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| Ligand Name: N-[(1R)-1-[2-chloro-4-(4-fluorophenyl)phenyl]-2-imidazol-1-ylethyl]-4-[5-[3-fluoro-5-(5-fluoropyrimidin-4-yl)phenyl]-1,3,4-oxadiazol-2-yl]benzamide | Ligand Info | |||||
| Structure Description | Human sterol 14a-demethylase (CYP51) in complex with the functionally irreversible inhibitor (R)-N-(1-(3-chloro-4'-fluoro-[1,1'-biphenyl]-4-yl)-2-(1H-imidazol-1-yl)ethyl)-4-(5-(3-fluoro-5-(5-fluoropyrimidin-4-yl)phenyl)-1,3,4-oxadiazol-2-yl)benzamide | PDB:6Q2T | ||||
| Method | X-ray diffraction | Resolution | 2.80 Å | Mutation | No | [2] |
| PDB Sequence |
GKLPPYIFSP
67 IPFLGHAIAF77 GKSPIEFLEN87 AYEKYGPVFS97 FTMVGKTFTY107 LLGSDAAALL 117 FNSKNEDLNA127 EDVYSRLTTP137 VFGKGVAYDV147 PNPVFLEQKK157 MLKSGLNIAH 167 FKQHVSIIEK177 ETKEYFESWG187 ESGEKNVFEA197 LSELIILTAS207 HCLHGKEIRS 217 QLNEKVAQLY227 ADLDGGFSHA237 AWLLPGWLPL247 PSFRRRDRAH257 REIKDIFYKA 267 IQKRRQSQEK277 IDDILQTLLD287 ATYKDGRPLT297 DDEVAGMLIG307 LLLAGQHTSS 317 TTSAWMGFFL327 ARDKTLQKKC337 YLEQKTVCGE347 NLPPLTYDQL357 KDLNLLDRCI 367 KETLRLRPPI377 MIMMRMARTP387 QTVAGYTIPP397 GHQVCVSPTV407 NQRLKDSWVE 417 RLDFNPDRYL427 QDNPASGEKF437 AYVPFGAGRH447 RCIGENFAYV457 QIKTIWSTML 467 RLYEFDLIDG477 YFPTVNYTTM487 IHTPENPVIR497 YKRRS
|
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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 .PJM or .PJM2 or .PJM3 or :3PJM;style chemicals stick;color identity;select .A:70 or .A:77 or .A:100 or .A:101 or .A:102 or .A:103 or .A:105 or .A:130 or .A:131 or .A:134 or .A:135 or .A:139 or .A:143 or .A:144 or .A:145 or .A:152 or .A:159 or .A:234 or .A:236 or .A:239 or .A:304 or .A:306 or .A:307 or .A:308 or .A:310 or .A:311 or .A:315 or .A:377 or .A:381 or .A:400 or .A:449 or .A:487; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
PHE70
3.695
PHE77
3.942
MET100
4.939
VAL101
4.205
GLY102
4.138
LYS103
4.563
PHE105
3.940
VAL130
3.206
TYR131
3.266
LEU134
3.274
THR135
3.808
PHE139
2.952
VAL143
4.451
ALA144
4.694
TYR145
4.381
PHE152
3.962
|
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| Ligand Name: N-[(1r)-1-(3,4'-Difluorobiphenyl-4-Yl)-2-(1h-Imidazol-1-Yl)ethyl]-4-(5-Phenyl-1,3,4-Oxadiazol-2-Yl)benzamide | Ligand Info | |||||
| Structure Description | HUMAN STEROL 14-ALPHA DEMETHYLASE (CYP51) IN COMPLEX WITH VFV IN C121 SPACE GROUP | PDB:4UHI | ||||
| Method | X-ray diffraction | Resolution | 2.04 Å | Mutation | No | [4] |
| PDB Sequence |
PPYIFSPIPF
70 LGHAIAFGKS80 PIEFLENAYE90 KYGPVFSFTM100 VGKTFTYLLG110 SDAAALLFNS 120 KNEDLNAEDV130 YSRLTTPVFG140 KGVAYDVPNP150 VFLEQKKMLK160 SGLNIAHFKQ 170 HVSIIEKETK180 EYFESWGESG190 EKNVFEALSE200 LIILTASHCL210 HGKEIRSQLN 220 EKVAQLYADL230 DGGFSHAAWL240 LPGWLPLPSF250 RRRDRAHREI260 KDIFYKAIQK 270 RRQSQEKIDD280 ILQTLLDATY290 KDGRPLTDDE300 VAGMLIGLLL310 AGQHTSSTTS 320 AWMGFFLARD330 KTLQKKCYLE340 QKTVCGENLP350 PLTYDQLKDL360 NLLDRCIKET 370 LRLRPPIMIM380 MRMARTPQTV390 AGYTIPPGHQ400 VCVSPTVNQR410 LKDSWVERLD 420 FNPDRYLQDN430 PASGEKFAYV440 PFGAGRHRCI450 GENFAYVQIK460 TIWSTMLRLY 470 EFDLIDGYFP480 TVNYTTMIHT490 PENPVIRYKR500 RS
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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 .VFV or .VFV2 or .VFV3 or :3VFV;style chemicals stick;color identity;select .A:71 or .A:74 or .A:77 or .A:98 or .A:100 or .A:101 or .A:105 or .A:107 or .A:130 or .A:131 or .A:134 or .A:135 or .A:139 or .A:143 or .A:144 or .A:145 or .A:152 or .A:159 or .A:234 or .A:235 or .A:236 or .A:239 or .A:240 or .A:303 or .A:304 or .A:307 or .A:308 or .A:310 or .A:311 or .A:315 or .A:376 or .A:377 or .A:379 or .A:381 or .A:400 or .A:402 or .A:449 or .A:487 or .A:488; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
LEU71
4.420
ALA74
4.946
PHE77
3.281
PHE98
4.376
MET100
3.526
VAL101
3.513
PHE105
3.494
TYR107
2.753
VAL130
4.277
TYR131
3.641
LEU134
3.336
THR135
3.698
PHE139
3.393
VAL143
4.629
ALA144
3.992
TYR145
4.309
PHE152
3.368
LEU159
3.195
PHE234
3.389
SER235
3.779
|
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| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| References | Top | ||||
|---|---|---|---|---|---|
| REF 1 | Structural basis of human CYP51 inhibition by antifungal azoles. J Mol Biol. 2010 Apr 9;397(4):1067-78. | ||||
| REF 2 | Validation of Human Sterol 14Alpha-Demethylase (CYP51) Druggability: Structure-Guided Design, Synthesis, and Evaluation of Stoichiometric, Functionally Irreversible Inhibitors. J Med Chem. 2019 Nov 27;62(22):10391-10401. | ||||
| REF 3 | A requirement for an active proton delivery network supports a compound I-mediated C-C bond cleavage in CYP51 catalysis. J Biol Chem. 2020 Jul 17;295(29):9998-10007. | ||||
| REF 4 | Human sterol 14Alpha-demethylase as a target for anticancer chemotherapy: towards structure-aided drug design. J Lipid Res. 2016 Aug;57(8):1552-63. | ||||
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