Binding Site Information of Target
| Target General Information | Top | ||||
|---|---|---|---|---|---|
| Target ID | T59056 | Target Info | |||
| Target Name | Aldosterone synthase (CYP11B2) | ||||
| Synonyms | Steroid 18hydroxylase; Cytochrome P450C18; Cytochrome P450Aldo; Cytochrome P450 11B2, mitochondrial; CYPXIB2; CYP11B2; Aldosteronesynthesizing enzyme; ALDOS | ||||
| Target Type | Clinical trial Target | ||||
| Gene Name | CYP11B2 | ||||
| Biochemical Class | Paired donor oxygen oxidoreductase | ||||
| UniProt ID | |||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| Ligand Name: Osilodrostat | Ligand Info | |||||
| Structure Description | Human CYP11B2 in complex with LCI699 | PDB:7M8V | ||||
| Method | X-ray diffraction | Resolution | 3.08 Å | Mutation | No | [1] |
| PDB Sequence |
PRTVLPFEAM
41 PQHPGNRWLR51 LLQIWREQGY61 EHLHLEMHQT71 FQELGPIFRY81 NLRMVCVMLP 94 EDVEKLQQVD104 SLHPCRMILE114 PWVAYRQHRG124 HKCGVFLLNG134 PEWRFNRLRL 144 NPDVLSPKAV154 QRFLPMVDAV164 ARDFSQALKK174 KVLQNARGSL184 TLDVQPSIFH 194 YTIEASNLAL204 FGERLGLVGH214 SPSSASLNFL224 HALEVMFKST234 VQLMFMPRSL 244 SRWISPKVWK254 EHFEAWDCIF264 QYGDNCIQKI274 YQELAFNRPQ284 HYTGIVAELL 294 LKAELSLEAI304 KANSMELTAG314 SVDTTAFPLL324 MTLFELARNP334 DVQQILRQES 344 LAAAASISEH354 PQKATTELPL364 LRAALKETLR374 LYPVGLFLER384 VVSSDLVLQN 394 YHIPAGTLVQ404 VFLYSLGRNA414 ALFPRPERYN424 PQRWLDIRNF438 HHVPFGFGMR 448 QCLGRRLAEA458 EMLLLLHHVL468 KHFLVETLTQ478 EDIKMVYSFI488 LRPGTSPLLT 498 FRAI
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| Ligand Name: Deoxycorticosterone | Ligand Info | |||||
| Structure Description | Structure of human aldosterone synthase, CYP11B2, in complex with deoxycorticosterone | PDB:4DVQ | ||||
| Method | X-ray diffraction | Resolution | 2.49 Å | Mutation | No | [2] |
| PDB Sequence |
TVLPFEAMPQ
43 HPGNRWLRLL53 QIWREQGYEH63 LHLEMHQTFQ73 ELGPIFRYNL83 GGPRMVCVML 93 PEDVEKLQQV103 DSLHPCRMIL113 EPWVAYRQHR123 GHKCGVFLLN133 GPEWRFNRLR 143 LNPDVLSPKA153 VQRFLPMVDA163 VARDFSQALK173 KKVLQNARGS183 LTLDVQPSIF 193 HYTIEASNLA203 LFGERLGLVG213 HSPSSASLNF223 LHALEVMFKS233 TVQLMFMPRS 243 LSRWISPKVW253 KEHFEAWDCI263 FQYGDNCIQK273 IYQELAFNRP283 QHYTGIVAEL 293 LLKAELSLEA303 IKANSMELTA313 GSVDTTAFPL323 LMTLFELARN333 PDVQQILRQE 343 SLAAAASISE353 HPQKATTELP363 LLRAALKETL373 RLYPVGLFLE383 RVVSSDLVLQ 393 NYHIPAGTLV403 QVFLYSLGRN413 AALFPRPERY423 NPQRWLDIFH439 HVPFGFGMRQ 449 CLGRRLAEAE459 MLLLLHHVLK469 HFLVETLTQE479 DIKMVYSFIL489 RPGTSPLLTF 499 RAI
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| Ligand Name: R-fadrozole | Ligand Info | |||||
| Structure Description | Structure of human aldosterone synthase, CYP11B2, in complex with fadrozole | PDB:4FDH | ||||
| Method | X-ray diffraction | Resolution | 2.71 Å | Mutation | No | [2] |
| PDB Sequence |
TVLPFEAMPQ
43 HPGNRWLRLL53 QIWREQGYEH63 LHLEMHQTFQ73 ELGPIFRYNL83 GGPRMVCVML 93 PEDVEKLQQV103 DSLHPCRMIL113 EPWVAYRQHR123 GHKCGVFLLN133 GPEWRFNRLR 143 LNPDVLSPKA153 VQRFLPMVDA163 VARDFSQALK173 KKVLQNARGS183 LTLDVQPSIF 193 HYTIEASNLA203 LFGERLGLVG213 HSPSSASLNF223 LHALEVMFKS233 TVQLMFMPRS 243 LSRWISPKVW253 KEHFEAWDCI263 FQYGDNCIQK273 IYQELAFNRP283 QHYTGIVAEL 293 LLKAELSLEA303 IKANSMELTA313 GSVDTTAFPL323 LMTLFELARN333 PDVQQILRQE 343 SLAAAASISE353 HPQKATTELP363 LLRAALKETL373 RLYPVGLFLE383 RVVSSDLVLQ 393 NYHIPAGTLV403 QVFLYSLGRN413 AALFPRPERY423 NPQRWLDNFH439 HVPFGFGMRQ 449 CLGRRLAEAE459 MLLLLHHVLK469 HFLVETLTQE479 DIKMVYSFIL489 RPGTSPLLTF 499 RAI
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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 .0T3 or .0T32 or .0T33 or :30T3;style chemicals stick;color identity;select .A:116 or .A:120 or .A:130 or .A:230 or .A:231 or .A:260 or .A:309 or .A:310 or .A:313 or .A:314 or .A:318 or .A:450 or .A:487 or .A:488; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Ligand Name: 5-Chloranyl-3,3-dimethyl-2-[5-[1-(1-methylpyrazol-4-yl)carbonylazetidin-3-yl]oxypyridin-3-yl]isoindol-1-one | Ligand Info | |||||
| Structure Description | Structure of aldosterone synthase (CYP11B2) in complex with 5-chloro-3,3-dimethyl-2-[5-[1-(1-methylpyrazole-4-carbonyl)azetidin-3-yl]oxy-3-pyridyl]isoindolin-1-one | PDB:6XZ9 | ||||
| Method | X-ray diffraction | Resolution | 2.77 Å | Mutation | No | [3] |
| PDB Sequence |
TVLPFEAMPQ
43 HPGNRWLRLL53 QIWREQGYEH63 LHLEMHQTFQ73 ELGPIFRYNL83 GGPRMVCVML 93 PEDVEKLQQV103 DSLHPCRMIL113 EPWVAYRQHR123 GHKCGVFLLN133 GPEWRFNRLR 143 LNPDVLSPKA153 VQRFLPMVDA163 VARDFSQALK173 KKVLQNARGS183 LTLDVQPSIF 193 HYTIEASNLA203 LFGERLGLVG213 HSPSSASLNF223 LHALEVMFKS233 TVQLMFMPRS 243 LSRWISPKVW253 KEHFEAWDCI263 FQYGDNCIQK273 IYQELAFNRP283 QHYTGIVAEL 293 LLKAELSLEA303 IKANSMELTA313 GSVDTTAFPL323 LMTLFELARN333 PDVQQILRQE 343 SLAAAASISE353 HPQKATTELP363 LLRAALKETL373 RLYPVGLFLE383 RVVSSDLVLQ 393 NYHIPAGTLV403 QVFLYSLGRN413 AALFPRPERY423 NPQRWLDNFH439 HVPFGFGMRQ 449 CLGRRLAEAE459 MLLLLHHVLK469 HFLVETLTQE479 DIKMVYSFIL489 RPGTSPLLTF 499 RAIN
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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 .O4W or .O4W2 or .O4W3 or :3O4W;style chemicals stick;color identity;select .A:116 or .A:120 or .A:130 or .A:227 or .A:230 or .A:231 or .A:238 or .A:239 or .A:260 or .A:263 or .A:309 or .A:310 or .A:313 or .A:314 or .A:318 or .A:378 or .A:379 or .A:380 or .A:381 or .A:383 or .A:404 or .A:450 or .A:485 or .A:487 or .A:488; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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TRP116
3.654
ARG120
3.877
PHE130
3.587
LEU227
4.257
MET230
3.879
PHE231
3.146
MET238
3.633
PHE239
4.975
TRP260
3.297
ILE263
4.733
MET309
4.088
GLU310
3.412
ALA313
3.489
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| Ligand Name: Ferroheme c(2-) | Ligand Info | |||||
| Structure Description | Structure of aldosterone synthase (CYP11B2) in complex with 5-chloro-3,3-dimethyl-2-[5-[1-(1-methylpyrazole-4-carbonyl)azetidin-3-yl]oxy-3-pyridyl]isoindolin-1-one | PDB:6XZ9 | ||||
| Method | X-ray diffraction | Resolution | 2.77 Å | Mutation | No | [3] |
| PDB Sequence |
TVLPFEAMPQ
43 HPGNRWLRLL53 QIWREQGYEH63 LHLEMHQTFQ73 ELGPIFRYNL83 GGPRMVCVML 93 PEDVEKLQQV103 DSLHPCRMIL113 EPWVAYRQHR123 GHKCGVFLLN133 GPEWRFNRLR 143 LNPDVLSPKA153 VQRFLPMVDA163 VARDFSQALK173 KKVLQNARGS183 LTLDVQPSIF 193 HYTIEASNLA203 LFGERLGLVG213 HSPSSASLNF223 LHALEVMFKS233 TVQLMFMPRS 243 LSRWISPKVW253 KEHFEAWDCI263 FQYGDNCIQK273 IYQELAFNRP283 QHYTGIVAEL 293 LLKAELSLEA303 IKANSMELTA313 GSVDTTAFPL323 LMTLFELARN333 PDVQQILRQE 343 SLAAAASISE353 HPQKATTELP363 LLRAALKETL373 RLYPVGLFLE383 RVVSSDLVLQ 393 NYHIPAGTLV403 QVFLYSLGRN413 AALFPRPERY423 NPQRWLDNFH439 HVPFGFGMRQ 449 CLGRRLAEAE459 MLLLLHHVLK469 HFLVETLTQE479 DIKMVYSFIL489 RPGTSPLLTF 499 RAIN
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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 .HEC or .HEC2 or .HEC3 or :3HEC;style chemicals stick;color identity;select .A:110 or .A:129 or .A:130 or .A:137 or .A:141 or .A:310 or .A:311 or .A:314 or .A:315 or .A:318 or .A:319 or .A:322 or .A:373 or .A:378 or .A:379 or .A:381 or .A:382 or .A:383 or .A:384 or .A:407 or .A:442 or .A:443 or .A:444 or .A:445 or .A:447 or .A:448 or .A:449 or .A:450 or .A:451 or .A:452 or .A:453 or .A:455 or .A:456 or .A:460; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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ARG110
2.697
VAL129
3.139
PHE130
3.542
TRP137
3.135
ARG141
2.728
GLU310
3.991
LEU311
3.579
GLY314
3.664
SER315
3.274
THR318
3.063
THR319
3.252
PRO322
3.626
LEU373
3.933
VAL378
3.522
GLY379
4.232
PHE381
4.384
LEU382
3.446
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| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Ligand Name: N-[(1R)-1-[5-(6-chloro-1,1-dimethyl-3-oxoisoindol-2-yl)pyridin-3-yl]ethyl]methanesulfonamide | Ligand Info | |||||
| Structure Description | Structure of aldosterone synthase (CYP11B2) in complex with N-[(1R)-1-[5-(6-chloro-1,1-dimethyl-3-oxo-isoindolin-2-yl)-3-pyridyl]ethyl]methanesulfonamide | PDB:6XZ8 | ||||
| Method | X-ray diffraction | Resolution | 3.00 Å | Mutation | No | [3] |
| PDB Sequence |
TVLPFEAMPQ
43 HPGNRWLRLL53 QIWREQGYEH63 LHLEMHQTFQ73 ELGPIFRYNL83 GGPRMVCVML 93 PEDVEKLQQV103 DSLHPCRMIL113 EPWVAYRQHR123 GHKCGVFLLN133 GPEWRFNRLR 143 LNPDVLSPKA153 VQRFLPMVDA163 VARDFSQALK173 KKVLQNARGS183 LTLDVQPSIF 193 HYTIEASNLA203 LFGERLGLVG213 HSPSSASLNF223 LHALEVMFKS233 TVQLMFMPRS 243 LSRWISPKVW253 KEHFEAWDCI263 FQYGDNCIQK273 IYQELAFNRP283 QHYTGIVAEL 293 LLKAELSLEA303 IKANSMELTA313 GSVDTTAFPL323 LMTLFELARN333 PDVQQILRQE 343 SLAAAASISE353 HPQKATTELP363 LLRAALKETL373 RLYPVGLFLE383 RVVSSDLVLQ 393 NYHIPAGTLV403 QVFLYSLGRN413 AALFPRPERY423 NPQRWLDINF438 HHVPFGFGMR 448 QCLGRRLAEA458 EMLLLLHHVL468 KHFLVETLTQ478 EDIKMVYSFI488 LRPGTSPLLT 498 FRAIN
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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 .O4T or .O4T2 or .O4T3 or :3O4T;style chemicals stick;color identity;select .A:116 or .A:120 or .A:130 or .A:227 or .A:230 or .A:231 or .A:260 or .A:309 or .A:310 or .A:313 or .A:314 or .A:318 or .A:378 or .A:379 or .A:380 or .A:381 or .A:450 or .A:487 or .A:488; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
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| Ligand Name: N-[(8r)-4-(4-Chloro-3-Fluorophenyl)-5,6,7,8-Tetrahydroisoquinolin-8-Yl]propanamide | Ligand Info | |||||
| Structure Description | Structure of aldosterone synthase (CYP11B2) in complex with (+)-(R)-N-(4-(4-chloro-3-fluorophenyl)-5,6,7,8-tetrahydroisoquinolin-8-yl)propionamide | PDB:4ZGX | ||||
| Method | X-ray diffraction | Resolution | 3.20 Å | Mutation | No | [4] |
| PDB Sequence |
TVLPFEAMPQ
43 HPGNRWLRLL53 QIWREQGYEH63 LHLEMHQTFQ73 ELGPIFRYNL83 GGPRMVCVML 93 PEDVEKLQQV103 DSLHPCRMIL113 EPWVAYRQHR123 GHKCGVFLLN133 GPEWRFNRLR 143 LNPDVLSPKA153 VQRFLPMVDA163 VARDFSQALK173 KKVLQNARGS183 LTLDVQPSIF 193 HYTIEASNLA203 LFGERLGLVG213 HSPSSASLNF223 LHALEVMFKS233 TVQLMFMPRS 243 LSRWISPKVW253 KEHFEAWDCI263 FQYGDNCIQK273 IYQELAFNRP283 QHYTGIVAEL 293 LLKAELSLEA303 IKANSMELTA313 GSVDTTAFPL323 LMTLFELARN333 PDVQQILRQE 343 SLAAAASISE353 HPQKATTELP363 LLRAALKETL373 RLYPVGLFLE383 RVVSSDLVLQ 393 NYHIPAGTLV403 QVFLYSLGRN413 AALFPRPERY423 NPQRWLDINF438 HHVPFGFGMR 448 QCLGRRLAEA458 EMLLLLHHVL468 KHFLVETLTQ478 EDIKMVYSFI488 LRPGTSPLLT 498 FRAIN
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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 .QHC or .QHC2 or .QHC3 or :3QHC;style chemicals stick;color identity;select .A:116 or .A:120 or .A:130 or .A:230 or .A:231 or .A:260 or .A:310 or .A:313 or .A:314 or .A:318 or .A:378 or .A:379 or .A:380 or .A:381 or .A:382 or .A:407 or .A:442 or .A:450 or .A:487 or .A:488; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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TRP116
3.466
ARG120
4.544
PHE130
3.570
MET230
4.710
PHE231
3.951
TRP260
3.695
GLU310
3.277
ALA313
4.133
GLY314
3.648
THR318
3.761
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| References | Top | ||||
|---|---|---|---|---|---|
| REF 1 | Aldosterone Synthase Structure With Cushing Disease Drug LCI699 Highlights Avenues for Selective CYP11B Drug Design. Hypertension. 2021 Sep;78(3):751-759. | ||||
| REF 2 | Structural insights into aldosterone synthase substrate specificity and targeted inhibition. Mol Endocrinol. 2013 Feb;27(2):315-24. | ||||
| REF 3 | Discovery of 3-Pyridyl Isoindolin-1-one Derivatives as Potent, Selective, and Orally Active Aldosterone Synthase (CYP11B2) Inhibitors. J Med Chem. 2020 Jul 9;63(13):6876-6897. | ||||
| REF 4 | Discovery of 4-Aryl-5,6,7,8-tetrahydroisoquinolines as Potent, Selective, and Orally Active Aldosterone Synthase (CYP11B2) Inhibitors: In Vivo Evaluation in Rodents and Cynomolgus Monkeys. J Med Chem. 2015 Oct 22;58(20):8054-65. | ||||
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