Binding Site Information of Target
| Target General Information | Top | ||||
|---|---|---|---|---|---|
| Target ID | T17852 | Target Info | |||
| Target Name | Phosphodiesterase 9 (PDE9) | ||||
| Synonyms | High affinity cGMPspecific 3',5'cyclic phosphodiesterase 9A; High affinity cGMP-specific 3',5'-cyclic phosphodiesterase 9A | ||||
| Target Type | Clinical trial Target | ||||
| Gene Name | PDE9A | ||||
| Biochemical Class | Phosphoric diester hydrolase | ||||
| UniProt ID | |||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| Ligand Name: PF-4447943 | Ligand Info | |||||
| Structure Description | Human phosphodiesterase 9 in complex with inhibitors | PDB:4E90 | ||||
| Method | X-ray diffraction | Resolution | 2.50 Å | Mutation | No | [1] |
| PDB Sequence |
GSHMTYPKYL
187 LSPETIEALR197 KPTFDVWLWE207 PNEMLSCLEH217 MYHDLGLVRD227 FSINPVTLRR 237 WLFCVHDNYR247 NNPFHNFRHC257 FCVAQMMYSM267 VWLCSLQEKF277 SQTDILILMT 287 AAICHDLDHP297 GYNNTYQINA307 RTELAVRYND317 ISPLENHHCA327 VAFQILAEPE 337 CNIFSNIPPD347 GFKQIRQGMI357 TLILATDMAR367 HAEIMDSFKE377 KMENFDYSNE 387 EHMTLLKMIL397 IKCCDISNEV407 RPMEVAEPWV417 DCLLEEYFMQ427 SDREKSEGLP 437 VAPFMDRDKV447 TKATAQIGFI457 KFVLIPMFET467 VTKLFPMVEE477 IMLQPLWESR 487 DRYEELKRID497 DAMKELQK
|
|||||
|
|
||||||
| Ligand Name: Cyclic Guanosine Monophosphate | Ligand Info | |||||
| Structure Description | human phosphodiestrase 9 in complex with cGMP (Zn inhibited) | PDB:3DYN | ||||
| Method | X-ray diffraction | Resolution | 2.10 Å | Mutation | No | [2] |
| PDB Sequence |
GSHMTYPKYL
187 LSPETIEALR197 KPTFDVWLWE207 PNEMLSCLEH217 MYHDLGLVRD227 FSINPVTLRR 237 WLFCVHDNYR247 NNPFHNFRHC257 FCVAQMMYSM267 VWLCSLQEKF277 SQTDILILMT 287 AAICHDLDHP297 GYNNTYQINA307 RTELAVRYND317 ISPLENHHCA327 VAFQILAEPE 337 CNIFSNIPPD347 GFKQIRQGMI357 TLILATDMAR367 HAEIMDSFKE377 KMENFDYSNE 387 EHMTLLKMIL397 IKCCDISNEV407 RPMEVAEPWV417 DCLLEEYFMQ427 SDREKSEGLP 437 VAPFMDRDKV447 TKATAQIGFI457 KFVLIPMFET467 VTKLFPMVEE477 IMLQPLWESR 487 DRYEELKRID497 DAMKELQK
|
|||||
|
|
||||||
| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Ligand Name: Guanosine-5'-Monophosphate | Ligand Info | |||||
| Structure Description | Human Phosphodiesterase 9 in complex with product 5'-GMP (E+P complex) | PDB:3DY8 | ||||
| Method | X-ray diffraction | Resolution | 2.15 Å | Mutation | No | [2] |
| PDB Sequence |
GSHMTYPKYL
187 LSPETIEALR197 KPTFDVWLWE207 PNEMLSCLEH217 MYHDLGLVRD227 FSINPVTLRR 237 WLFCVHDNYR247 NNPFHNFRHC257 FCVAQMMYSM267 VWLCSLQEKF277 SQTDILILMT 287 AAICHDLDHP297 GYNNTYQINA307 RTELAVRYND317 ISPLENHHCA327 VAFQILAEPE 337 CNIFSNIPPD347 GFKQIRQGMI357 TLILATDMAR367 HAEIMDSFKE377 KMENFDYSNE 387 EHMTLLKMIL397 IKCCDISNEV407 RPMEVAEPWV417 DCLLEEYFMQ427 SDREKSEGLP 437 VAPFMDRDKV447 TKATAQIGFI457 KFVLIPMFET467 VTKLFPMVEE477 IMLQPLWESR 487 DRYEELKRID497 DAMKELQK
|
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .5GP or .5GP2 or .5GP3 or :35GP;style chemicals stick;color identity;select .A:251 or .A:252 or .A:256 or .A:292 or .A:293 or .A:296 or .A:363 or .A:365 or .A:402 or .A:403 or .A:405 or .A:406 or .A:420 or .A:424 or .A:452 or .A:453 or .A:456; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
||||||
| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Ligand Name: Isobutylmethylxanthine | Ligand Info | |||||
| Structure Description | Crystal structure of PDE9 in complex with IBMX | PDB:2HD1 | ||||
| Method | X-ray diffraction | Resolution | 2.23 Å | Mutation | No | [3] |
| PDB Sequence |
PTYPKYLLSP
190 ETIEALRKPT200 FDVWLWEPNE210 MLSCLEHMYH220 DLGLVRDFSI230 NPVTLRRWLF 240 CVHDNYRNNP250 FHNFRHCFCV260 AQMMYSMVWL270 CSLQEKFSQT280 DILILMTAAI 290 CHDLDHPGYN300 NTYQINARTE310 LAVRYNDISP320 LENHHCAVAF330 QILAEPECNI 340 FSNIPPDGFK350 QIRQGMITLI360 LATDMARHAE370 IMDSFKEKME380 NFDYSNEEHM 390 TLLKMILIKC400 CDISNEVRPM410 EVAEPWVDCL420 LEEYFMQSDR430 EKSEGLPVAP 440 FMDRDKVTKA450 TAQIGFIKFV460 LIPMFETVTK470 LFPMVEEIML480 QPLWESRDRY 490 EELKRIDDAM500 KELQKK
|
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .IBM or .IBM2 or .IBM3 or :3IBM;style chemicals stick;color identity;select .A:251 or .A:252 or .A:365 or .A:402 or .A:403 or .A:404 or .A:405 or .A:406 or .A:420 or .A:424 or .A:452 or .A:453 or .A:456; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
||||||
| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Ligand Name: 6-[[(1S)-1-(4-Chlorophenyl)ethyl]amino]-1-cyclopentyl-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one | Ligand Info | |||||
| Structure Description | Crystal structure of PDE9 in complex with racemic inhibitor C33 | PDB:4Y86 | ||||
| Method | X-ray diffraction | Resolution | 2.01 Å | Mutation | No | [4] |
| PDB Sequence |
KYLLSPETIE
194 ALRKPTFDVW204 LWEPNEMLSC214 LEHMYHDLGL224 VRDFSINPVT234 LRRWLFCVHD 244 NYRNNPFHNF254 RHCFCVAQMM264 YSMVWLCSLQ274 EKFSQTDILI284 LMTAAICHDL 294 DHPGYNNTYQ304 INARTELAVR314 YNDISPLENH324 HCAVAFQILA334 EPECNIFSNI 344 PPDGFKQIRQ354 GMITLILATD364 MARHAEIMDS374 FKEKMENFDY384 SNEEHMTLLK 394 MILIKCCDIS404 NEVRPMEVAE414 PWVDCLLEEY424 FMQSDREKSE434 GLPVAPFMDR 444 DKVTKATAQI454 GFIKFVLIPM464 FETVTKLFPM474 VEEIMLQPLW484 ESRDRYEELK 494 RIDDAMKELQ504 KK
|
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .49D or .49D2 or .49D3 or :349D;style chemicals stick;color identity;select .A:251 or .A:252 or .A:365 or .A:402 or .A:403 or .A:405 or .A:406 or .A:420 or .A:421 or .A:424 or .A:425 or .A:441 or .A:442 or .A:447 or .A:452 or .A:453 or .A:456; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
||||||
| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Ligand Name: 4H-Pyrazolo(3,4-d)pyrimidin-4-one, 1-(2-chlorophenyl)-1,5-dihydro-6-((2R)-3,3,3-trifluoro-2-methylpropyl)- | Ligand Info | |||||
| Structure Description | Crystal structure of PDE9A(Q453E) in complex with inhibitor BAY73-6691 | PDB:3QI3 | ||||
| Method | X-ray diffraction | Resolution | 2.30 Å | Mutation | Yes | [5] |
| PDB Sequence |
PTYPKYLLSP
190 ETIEALRKPT200 FDVWLWEPNE210 MLSCLEHMYH220 DLGLVRDFSI230 NPVTLRRWLF 240 CVHDNYRNNP250 FHNFRHCFCV260 AQMMYSMVWL270 CSLQEKFSQT280 DILILMTAAI 290 CHDLDHPGYN300 NTYQINARTE310 LAVRYNDISP320 LENHHCAVAF330 QILAEPECNI 340 FSNIPPDGFK350 QIRQGMITLI360 LATDMARHAE370 IMDSFKEKME380 NFDYSNEEHM 390 TLLKMILIKC400 CDISNEVRPM410 EVAEPWVDCL420 LEEYFMQSDR430 EKSEGLPVAP 440 FMDRDKVTKA450 TAEIGFIKFV460 LIPMFETVTK470 LFPMVEEIML480 QPLWESRDRY 490 EELKRIDDAM500 KELQK
|
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .PDB or .PDB2 or .PDB3 or :3PDB;style chemicals stick;color identity;select .A:251 or .A:252 or .A:365 or .A:402 or .A:403 or .A:405 or .A:406 or .A:417 or .A:420 or .A:421 or .A:424 or .A:441 or .A:447 or .A:449 or .A:452 or .A:453 or .A:456; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
||||||
| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Ligand Name: 1-cyclopentyl-6-[[(2R)-1-(6-fluoranyl-2-azaspiro[3.3]heptan-2-yl)-1-oxidanylidene-propan-2-yl]amino]-5H-pyrazolo[3,4-d]pyrimidin-4-one | Ligand Info | |||||
| Structure Description | phosphodiesterase-9A in complex with inhibitor 4b | PDB:7F0I | ||||
| Method | X-ray diffraction | Resolution | 2.70 Å | Mutation | No | [6] |
| PDB Sequence |
LLSPETIEAL
196 RKPTFDVWLW206 EPNEMLSCLE216 HMYHDLGLVR226 DFSINPVTLR236 RWLFCVHDNY 246 RNNPFHNFRH256 CFCVAQMMYS266 MVWLCSLQEK276 FSQTDILILM286 TAAICHDLDH 296 PGYNNTYQIN306 ARTELAVRYN316 DISPLENHHC326 AVAFQILAEP336 ECNIFSNIPP 346 DGFKQIRQGM356 ITLILATDMA366 RHAEIMDSFK376 EKMENFDYSN386 EEHMTLLKMI 396 LIKCCDISNE406 VRPMEVAEPW416 VDCLLEEYFM426 QSDREKSEGL436 PVAPFMDRDK 446 VTKATAQIGF456 IKFVLIPMFE466 TVTKLFPMVE476 EIMLQPLWES486 RDRYEELKRI 496 DDAMKE
|
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .06A or .06A2 or .06A3 or :306A;style chemicals stick;color identity;select .A:251 or .A:252 or .A:365 or .A:402 or .A:403 or .A:405 or .A:406 or .A:420 or .A:421 or .A:424 or .A:441 or .A:452 or .A:453 or .A:456; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
||||||
| Ligand Name: 6-{[(1r)-1-(4-Chlorophenyl)ethyl]amino}-1-Cyclopentyl-1,5-Dihydro-4h-Pyrazolo[3,4-D]pyrimidin-4-One | Ligand Info | |||||
| Structure Description | Crystal structure of phosphodiesterase 9 in complex with (R)-C33 (6-{[(1R)-1-(4-chlorophenyl)ethyl]amino}-1-cyclopentyl-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one) | PDB:4Y87 | ||||
| Method | X-ray diffraction | Resolution | 3.10 Å | Mutation | No | [4] |
| PDB Sequence |
KYLLSPETIE
194 ALRKPTFDVW204 LWEPNEMLSC214 LEHMYHDLGL224 VRDFSINPVT234 LRRWLFCVHD 244 NYRNNPFHNF254 RHCFCVAQMM264 YSMVWLCSLQ274 EKFSQTDILI284 LMTAAICHDL 294 DHPGYNNTYQ304 INARTELAVR314 YNDISPLENH324 HCAVAFQILA334 EPECNIFSNI 344 PPDGFKQIRQ354 GMITLILATD364 MARHAEIMDS374 FKEKMENFDY384 SNEEHMTLLK 394 MILIKCCDIS404 NEVRPMEVAE414 PWVDCLLEEY424 FMQSDREKSE434 GLPVAPFMDR 444 DKVTKATAQI454 GFIKFVLIPM464 FETVTKLFPM474 VEEIMLQPLW484 ESRDRYEELK 494 RIDDAMKELQ504 KK
|
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .49E or .49E2 or .49E3 or :349E;style chemicals stick;color identity;select .A:251 or .A:252 or .A:365 or .A:402 or .A:403 or .A:405 or .A:406 or .A:420 or .A:421 or .A:424 or .A:441 or .A:452 or .A:453 or .A:456 or .A:460; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
||||||
| Ligand Name: 6-[(3s,4s)-1-Benzyl-4-Methylpyrrolidin-3-Yl]-1-(1-Methylethyl)-1,5-Dihydro-4h-Pyrazolo[3,4-D]pyrimidin-4-One | Ligand Info | |||||
| Structure Description | Human PDE9 in complex with selective inhibitor | PDB:3JSW | ||||
| Method | X-ray diffraction | Resolution | 2.30 Å | Mutation | No | [7] |
| PDB Sequence |
GSHMTYPKYL
187 LSPETIEALR197 KPTFDVWLWE207 PNEMLSCLEH217 MYHDLGLVRD227 FSINPVTLRR 237 WLFCVHDNYR247 NNPFHNFRHC257 FCVAQMMYSM267 VWLCSLQEKF277 SQTDILILMT 287 AAICHDLDHP297 GYNNTYQINA307 RTELAVRYND317 ISPLENHHCA327 VAFQILAEPE 337 CNIFSNIPPD347 GFKQIRQGMI357 TLILATDMAR367 HAEIMDSFKE377 KMENFDYSNE 387 EHMTLLKMIL397 IKCCDISNEV407 RPMEVAEPWV417 DCLLEEYFMQ427 SDREKSEGLP 437 VAPFMDRDKV447 TKATAQIGFI457 KFVLIPMFET467 VTKLFPMVEE477 IMLQPLWESR 487 DRYEELKRID497 DAMKELQK
|
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .JAR or .JAR2 or .JAR3 or :3JAR;style chemicals stick;color identity;select .A:251 or .A:252 or .A:365 or .A:402 or .A:403 or .A:405 or .A:406 or .A:417 or .A:420 or .A:421 or .A:424 or .A:441 or .A:452 or .A:453 or .A:456 or .A:460; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
||||||
| Ligand Name: 1-Cyclopentyl-6-[(1r)-1-(3-Phenoxyazetidin-1-Yl)ethyl]-1,5-Dihydro-4h-Pyrazolo[3,4-D]pyrimidin-4-One | Ligand Info | |||||
| Structure Description | Human pde9 in complex with selective compound | PDB:4G2J | ||||
| Method | X-ray diffraction | Resolution | 2.40 Å | Mutation | No | [1] |
| PDB Sequence |
GSHMTYPKYL
187 LSPETIEALR197 KPTFDVWLWE207 PNEMLSCLEH217 MYHDLGLVRD227 FSINPVTLRR 237 WLFCVHDNYR247 NNPFHNFRHC257 FCVAQMMYSM267 VWLCSLQEKF277 SQTDILILMT 287 AAICHDLDHP297 GYNNTYQINA307 RTELAVRYND317 ISPLENHHCA327 VAFQILAEPE 337 CNIFSNIPPD347 GFKQIRQGMI357 TLILATDMAR367 HAEIMDSFKE377 KMENFDYSNE 387 EHMTLLKMIL397 IKCCDISNEV407 RPMEVAEPWV417 DCLLEEYFMQ427 SDREKSEGLP 437 VAPFMDRDKV447 TKATAQIGFI457 KFVLIPMFET467 VTKLFPMVEE477 IMLQPLWESR 487 DRYEELKRID497 DAMKELQK
|
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .0WF or .0WF2 or .0WF3 or :30WF;style chemicals stick;color identity;select .A:251 or .A:252 or .A:363 or .A:365 or .A:402 or .A:403 or .A:404 or .A:405 or .A:406 or .A:417 or .A:420 or .A:421 or .A:424 or .A:441 or .A:447 or .A:452 or .A:453 or .A:455 or .A:456 or .A:459 or .A:460; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
PHE251
3.547
HIS252
3.102
THR363
4.597
MET365
3.100
ASP402
4.322
ILE403
2.887
SER404
4.783
ASN405
3.965
GLU406
4.236
VAL417
3.590
LEU420
3.050
|
|||||
| Ligand Name: 6-Benzyl-1-cyclopentyl-1,5-dihydro-4h-pyrazolo[3,4-d]pyrimidin-4-one | Ligand Info | |||||
| Structure Description | Human phosphodiesterase 9 in complex with inhibitor | PDB:3JSI | ||||
| Method | X-ray diffraction | Resolution | 2.72 Å | Mutation | No | [7] |
| PDB Sequence |
GSHMTYPKYL
187 LSPETIEALR197 KPTFDVWLWE207 PNEMLSCLEH217 MYHDLGLVRD227 FSINPVTLRR 237 WLFCVHDNYR247 NNPFHNFRHC257 FCVAQMMYSM267 VWLCSLQEKF277 SQTDILILMT 287 AAICHDLDHP297 GYNNTYQINA307 RTELAVRYND317 ISPLENHHCA327 VAFQILAEPE 337 CNIFSNIPPD347 GFKQIRQGMI357 TLILATDMAR367 HAEIMDSFKE377 KMENFDYSNE 387 EHMTLLKMIL397 IKCCDISNEV407 RPMEVAEPWV417 DCLLEEYFMQ427 SDREKSEGLP 437 VAPFMDRDKV447 TKATAQIGFI457 KFVLIPMFET467 VTKLFPMVEE477 IMLQPLWESR 487 DRYEELKRID497 DAMKELQK
|
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .WTC or .WTC2 or .WTC3 or :3WTC;style chemicals stick;color identity;select .A:251 or .A:252 or .A:365 or .A:402 or .A:403 or .A:405 or .A:406 or .A:417 or .A:420 or .A:421 or .A:424 or .A:441 or .A:447 or .A:452 or .A:453 or .A:456 or .A:461; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
||||||
| Ligand Name: 1-Cyclopentyl-6-{(1r)-1-[3-(Pyrimidin-2-Yl)azetidin-1-Yl]ethyl}-1,5-Dihydro-4h-Pyrazolo[3,4-D]pyrimidin-4-One | Ligand Info | |||||
| Structure Description | Human PDE9 in complex with selective compound | PDB:4G2L | ||||
| Method | X-ray diffraction | Resolution | 3.00 Å | Mutation | No | [1] |
| PDB Sequence |
GSHMTYPKYL
187 LSPETIEALR197 KPTFDVWLWE207 PNEMLSCLEH217 MYHDLGLVRD227 FSINPVTLRR 237 WLFCVHDNYR247 NNPFHNFRHC257 FCVAQMMYSM267 VWLCSLQEKF277 SQTDILILMT 287 AAICHDLDHP297 GYNNTYQINA307 RTELAVRYND317 ISPLENHHCA327 VAFQILAEPE 337 CNIFSNIPPD347 GFKQIRQGMI357 TLILATDMAR367 HAEIMDSFKE377 KMENFDYSNE 387 EHMTLLKMIL397 IKCCDISNEV407 RPMEVAEPWV417 DCLLEEYFMQ427 SDREKSEGLP 437 VAPFMDRDKV447 TKATAQIGFI457 KFVLIPMFET467 VTKLFPMVEE477 IMLQPLWESR 487 DRYEELKRID497 DAMKELQK
|
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .0WL or .0WL2 or .0WL3 or :30WL;style chemicals stick;color identity;select .A:251 or .A:252 or .A:365 or .A:402 or .A:403 or .A:405 or .A:406 or .A:417 or .A:420 or .A:421 or .A:424 or .A:441 or .A:452 or .A:453 or .A:456; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
||||||
| Ligand Name: 1-(2-Chlorophenyl)-6-[(2s)-3,3,3-Trifluoro-2-Methylpropyl]-1,7-Dihydro-4h-Pyrazolo[3,4-D]pyrimidin-4-One | Ligand Info | |||||
| Structure Description | Crystal structure of the PDE9A catalytic domain in complex with (S)-BAY73-6691 | PDB:3K3H | ||||
| Method | X-ray diffraction | Resolution | 2.50 Å | Mutation | No | [8] |
| PDB Sequence |
YLLSPETIEA
195 LRKPTFDVWL205 WEPNEMLSCL215 EHMYHDLGLV225 RDFSINPVTL235 RRWLFCVHDN 245 YRNNPFHNFR255 HCFCVAQMMY265 SMVWLCSLQE275 KFSQTDILIL285 MTAAICHDLD 295 HPGYNNTYQI305 NARTELAVRY315 NDISPLENHH325 CAVAFQILAE335 PECNIFSNIP 345 PDGFKQIRQG355 MITLILATDM365 ARHAEIMDSF375 KEKMENFDYS385 NEEHMTLLKM 395 ILIKCCDISN405 EVRPMEVAEP415 WVDCLLEEYF425 MQSDREKSEG435 LPVAPFMDRD 445 KVTKATAQIG455 FIKFVLIPMF465 ETVTKLFPMV475 EEIMLQPLWE485 SRDRYEELKR 495 IDDAMKELQK505 K
|
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .BYE or .BYE2 or .BYE3 or :3BYE;style chemicals stick;color identity;select .A:251 or .A:252 or .A:365 or .A:402 or .A:403 or .A:405 or .A:406 or .A:417 or .A:420 or .A:421 or .A:424 or .A:441 or .A:447 or .A:452 or .A:453 or .A:456; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
||||||
| Ligand Name: N-(4-Methoxyphenyl)-N~2~-[1-(2-Methylphenyl)-4-Oxo-4,5-Dihydro-1h-Pyrazolo[3,4-D]pyrimidin-6-Yl]-L-Alaninamide | Ligand Info | |||||
| Structure Description | Crystal structure of the PDE9A catalytic domain in complex with inhibitor 28 | PDB:4GH6 | ||||
| Method | X-ray diffraction | Resolution | 2.70 Å | Mutation | No | [9] |
| PDB Sequence |
PTYPKYLLSP
190 ETIEALRKPT200 FDVWLWEPNE210 MLSCLEHMYH220 DLGLVRDFSI230 NPVTLRRWLF 240 CVHDNYRNNP250 FHNFRHCFCV260 AQMMYSMVWL270 CSLQEKFSQT280 DILILMTAAI 290 CHDLDHPGYN300 NTYQINARTE310 LAVRYNDISP320 LENHHCAVAF330 QILAEPECNI 340 FSNIPPDGFK350 QIRQGMITLI360 LATDMARHAE370 IMDSFKEKME380 NFDYSNEEHM 390 TLLKMILIKC400 CDISNEVRPM410 EVAEPWVDCL420 LEEYFMQSDR430 EKSEGLPVAP 440 FMDRDKVTKA450 TAQIGFIKFV460 LIPMFETVTK470 LFPMVEEIML480 QPLWESRDRY 490 EELKRIDDAM500 KELQKK
|
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .LUO or .LUO2 or .LUO3 or :3LUO;style chemicals stick;color identity;select .A:251 or .A:252 or .A:365 or .A:366 or .A:402 or .A:403 or .A:405 or .A:406 or .A:420 or .A:424 or .A:441 or .A:452 or .A:453 or .A:456 or .A:460; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
||||||
| Ligand Name: 1-cyclopentyl-6-[[(2R)-1-(2-oxa-6-azaspiro[3.3]heptan-6-yl)-1-oxidanylidene-propan-2-yl]amino]-5H-pyrazolo[3,4-d]pyrimidin-4-one | Ligand Info | |||||
| Structure Description | Crystal structure of the PDE9 catalytic domain in complex with inhibitor 4a | PDB:6LZZ | ||||
| Method | X-ray diffraction | Resolution | 2.40 Å | Mutation | No | [10] |
| PDB Sequence |
LLSPETIEAL
196 RKPTFDVWLW206 EPNEMLSCLE216 HMYHDLGLVR226 DFSINPVTLR236 RWLFCVHDNY 246 RNNPFHNFRH256 CFCVAQMMYS266 MVWLCSLQEK276 FSQTDILILM286 TAAICHDLDH 296 PGYNNTYQIN306 ARTELAVRYN316 DISPLENHHC326 AVAFQILAEP336 ECNIFSNIPP 346 DGFKQIRQGM356 ITLILATDMA366 RHAEIMDSFK376 EKMENFDYSN386 EEHMTLLKMI 396 LIKCCDISNE406 VRPMEVAEPW416 VDCLLEEYFM426 QSDREKSEGL436 PVAPFMDRDK 446 VTKATAQIGF456 IKFVLIPMFE466 TVTKLFPMVE476 EIMLQPLWES486 RDRYEELKRI 496 DDAMKELQKK506
|
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .EZU or .EZU2 or .EZU3 or :3EZU;style chemicals stick;color identity;select .A:251 or .A:252 or .A:365 or .A:402 or .A:403 or .A:405 or .A:406 or .A:420 or .A:424 or .A:441 or .A:452 or .A:453 or .A:456; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
||||||
| Ligand Name: Pde9-IN-1 | Ligand Info | |||||
| Structure Description | Crystal structure of the PDE9 catalytic domain in complex with inhibitor 2 | PDB:6A3N | ||||
| Method | X-ray diffraction | Resolution | 2.60 Å | Mutation | No | [11] |
| PDB Sequence |
KYLLSPETIE
194 ALRKPTFDVW204 LWEPNEMLSC214 LEHMYHDLGL224 VRDFSINPVT234 LRRWLFCVHD 244 NYRNNPFHNF254 RHCFCVAQMM264 YSMVWLCSLQ274 EKFSQTDILI284 LMTAAICHDL 294 DHPGYNNTYQ304 INARTELAVR314 YNDISPLENH324 HCAVAFQILA334 EPECNIFSNI 344 PPDGFKQIRQ354 GMITLILATD364 MARHAEIMDS374 FKEKMENFDY384 SNEEHMTLLK 394 MILIKCCDIS404 NEVRPMEVAE414 PWVDCLLEEY424 FMQSDREKSE434 GLPVAPFMDR 444 DKVTKATAQI454 GFIKFVLIPM464 FETVTKLFPM474 VEEIMLQPLW484 ESRDRYEELK 494 RIDDAMKELQ504 KK
|
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .9Q9 or .9Q92 or .9Q93 or :39Q9;style chemicals stick;color identity;select .A:251 or .A:252 or .A:365 or .A:402 or .A:403 or .A:406 or .A:420 or .A:424 or .A:441 or .A:452 or .A:453 or .A:456 or .A:461; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
||||||
| References | Top | ||||
|---|---|---|---|---|---|
| REF 1 | Application of structure-based drug design and parallel chemistry to identify selective, brain penetrant, in vivo active phosphodiesterase 9A inhibitors. J Med Chem. 2012 Nov 8;55(21):9055-68. | ||||
| REF 2 | Structural basis for the catalytic mechanism of human phosphodiesterase 9. Proc Natl Acad Sci U S A. 2008 Sep 9;105(36):13309-14. | ||||
| REF 3 | Crystal structure of phosphodiesterase 9 shows orientation variation of inhibitor 3-isobutyl-1-methylxanthine binding. Proc Natl Acad Sci U S A. 2004 Jun 29;101(26):9624-9. | ||||
| REF 4 | Structural Asymmetry of Phosphodiesterase-9A and a Unique Pocket for Selective Binding of a Potent Enantiomeric Inhibitor. Mol Pharmacol. 2015 Nov;88(5):836-45. | ||||
| REF 5 | Structural asymmetry of phosphodiesterase-9, potential protonation of a glutamic acid, and role of the invariant glutamine. PLoS One. 2011 Mar 31;6(3):e18092. | ||||
| REF 6 | Discovery of Potent Phosphodiesterase-9 Inhibitors for the Treatment of Hepatic Fibrosis. doi:10.1021/acs.jmedchem.1c00862. | ||||
| REF 7 | Identification of a brain penetrant PDE9A inhibitor utilizing prospective design and chemical enablement as a rapid lead optimization strategy. J Med Chem. 2009 Dec 24;52(24):7946-9. | ||||
| REF 8 | Insight into binding of phosphodiesterase-9A selective inhibitors by crystal structures and mutagenesis. J Med Chem. 2010 Feb 25;53(4):1726-31. | ||||
| REF 9 | Structure-based discovery of highly selective phosphodiesterase-9A inhibitors and implications for inhibitor design. J Med Chem. 2012 Oct 11;55(19):8549-58. | ||||
| REF 10 | Identification of phosphodiesterase-9 as a novel target for pulmonary arterial hypertension by using highly selective and orally bioavailable inhibitors | ||||
| REF 11 | Discovery of Potent, Selective, and Orally Bioavailable Inhibitors against Phosphodiesterase-9, a Novel Target for the Treatment of Vascular Dementia. J Med Chem. 2019 Apr 25;62(8):4218-4224. | ||||
If You Find Any Error in Data or Bug in Web Service, Please Kindly Report It to Dr. Zhou and Dr. Zhang.