Target Binding Site Detail
| Target General Information | Top | ||||
|---|---|---|---|---|---|
| Target ID | T10265 | Target Info | |||
| Target Name | Phosphodiesterase 4B (PDE4B) | ||||
| Synonyms | cAMP-specific 3',5'-cyclic phosphodiesterase 4B; Type 4B cAMP phosphodiesterase; Type 4 cyclic adenosine monophosphate phosphodiesterase (type 4 PDE); PDE32; DPDE4 | ||||
| Target Type | Clinical trial Target | ||||
| Gene Name | PDE4B | ||||
| Biochemical Class | Phosphoric diester hydrolase | ||||
| UniProt ID | |||||
| Ligand General Information | Top | ||||
|---|---|---|---|---|---|
| Ligand Name | Rolipram | Ligand Info | |||
| Canonical SMILES | COC1=C(C=C(C=C1)C2CC(=O)NC2)OC3CCCC3 | ||||
| InChI | 1S/C16H21NO3/c1-19-14-7-6-11(12-9-16(18)17-10-12)8-15(14)20-13-4-2-3-5-13/h6-8,12-13H,2-5,9-10H2,1H3,(H,17,18) | ||||
| InChIKey | HJORMJIFDVBMOB-UHFFFAOYSA-N | ||||
| PubChem Compound ID | 5092 | ||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| PDB ID: 4X0F Crystal structure of crosslink stabilized long-form PDE4B in complex with (R)-(-)-rolipram | ||||||
| Method | X-ray diffraction | Resolution | 3.22 Å | Mutation | Yes | [1] |
| PDB Sequence |
VTPFAQVLAS
175 LRSVRNNFTL223 EELDWALDQL233 ETIQTYRSVS243 EMASNKFKRM253 LNRELTHLSE 263 MSRCGNQVSE273 YISNTFLDKS326 RFGVNTENED336 HLAKELEDLN346 KWGLNIFNVA 356 GYSHNRPLTA366 IMYAIFQERD376 LLKTFRISSD386 TFITYMMTLE396 DHYHSDVAYH 406 NSLHAADVAQ416 STHVLLSTPA426 LDAVFTDLEI436 LAAIFAAAIH446 DVDHPGVSNQ 456 FLINTNSELA466 LMYNDESVLE476 NHHLAVGFKL486 LQEEHADIFM496 NLTKKQRQTL 506 RKMVIDMVLA516 TDMSKHMSLL526 ADLKTMVETK536 KVTSSGVLLL546 DNYTDRIQVL 556 RNMVHAADLS566 NPTKSLELYR576 QWTDRIMEEF586 FQQGDKERER596 GMEISPMADK 606 HTACVEKSQV616 GFIDYIVHPL626 WETWADLVQP636 DAQDILDTLE646 DNRNWYQAMI 656 P
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| PDB ID: 1XN0 Catalytic Domain Of Human Phosphodiesterase 4B In Complex With (R,S)-Rolipram | ||||||
| Method | X-ray diffraction | Resolution | 2.31 Å | Mutation | No | [2] |
| PDB Sequence |
EDHLAKELED
172 LNKWGLNIFN182 VAGYSHNRPL192 TIMYAIFQER203 DLLKTFRISS213 DTFITYMMTL 223 EDHYHSDVAY233 HNSLHAADVA243 QSTHVLLSTP253 ALDAVFTDLE263 ILAAIFAAAI 273 HDVDHPGVSN283 QFLINTNSEL293 ALMYNDESVL303 ENHHLAVGFK313 LLQEEHDIFM 324 NLTKKQRQTL334 RKMVIDMVLA344 TDMSKHMSLL354 ADLKTMVETK364 KVTSSGVLLL 374 DNYTDRIQVL384 RNMVHCADLS394 NPTKSLELYR404 QWTDRIMEEF414 FQQGDKERER 424 GMEISPMDKH435 TASVEKSQVG445 FIDYIVHPLW455 ETWADLVQPD465 AQDILDTLED 475 NRNWYQSMIP485
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| PDB ID: 1XMY Catalytic Domain Of Human Phosphodiesterase 4B In Complex With (R)-Rolipram | ||||||
| Method | X-ray diffraction | Resolution | 2.40 Å | Mutation | Yes | [2] |
| PDB Sequence |
> Chain A
EDHLAKELED 172 LNKWGLNIFN182 VAGYSHNRPL192 TIMYAIFQER203 DLLKTFRISS213 DTFITYMMTL 223 EDHYHSDVAY233 HNSLHAADVA243 QSTHVLLSTP253 ALDAVFTDLE263 ILAAIFAAAI 273 HDVDHPGVSN283 QFLINTNSEL293 ALMYNDESVL303 ENHHLAVGFK313 LLQEEHDIFM 324 NLTKKQRQTL334 RKMVIDMVLA344 TDMSKHMSLL354 ADLKTMVETK364 KVTSSGVLLL 374 DNYTDRIQVL384 RNMVHCADLS394 NPTKSLELYR404 QWTDRIMEEF414 FQQGDKERER 424 GMEISPMCDK434 HTASVEKSQV444 GFIDYIVHPL454 WETWADLVQP464 DAQDILDTLE 474 DNRNWYQSMI484 P> Chain B EDHLAKELED 172 LNKWGLNIFN182 VAGYSHNRPL192 TIMYAIFQER203 DLLKTFRISS213 DTFITYMMTL 223 EDHYHSDVAY233 HNSLHAADVA243 QSTHVLLSTP253 ALDAVFTDLE263 ILAAIFAAAI 273 HDVDHPGVSN283 QFLINTNSEL293 ALMYNDESVL303 ENHHLAVGFK313 LLQEEHCDIF 323 MNLTKKQRQT333 LRKMVIDMVL343 ATDMSKHMSL353 LADLKTMVET363 KKVTSSGVLL 373 LDNYTDRIQV383 LRNMVHCADL393 SNPTKSLELY403 RQWTDRIMEE413 FFQQGDKERE 423 RGMEISPMDK434 HTASVEKSQV444 GFIDYIVHPL454 WETWADLVQP464 DAQDILDTLE 474 DNRNWYQSMI484 P
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TYR233[A]
3.763
HIS234[A]
3.580
MET347[A]
4.244
ASP392[A]
4.607
LEU393[A]
4.334
ASN395[A]
3.512
TYR403[A]
4.141
TRP406[A]
4.115
THR407[A]
3.954
ILE410[A]
3.826
MET411[A]
3.782
PHE414[A]
3.966
MET431[A]
3.243
SER442[A]
3.937
GLN443[A]
3.024
PHE446[A]
3.334
|
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| PDB ID: 1RO6 Crystal structure of PDE4B2B complexed with Rolipram (R & S) | ||||||
| Method | X-ray diffraction | Resolution | 2.00 Å | Mutation | Yes | [3] |
| PDB Sequence |
SISRFGVNTE
161 NEDHLAKELE171 DLNKWGLNIF181 NVAGYSHNRP191 LTCIMYAIFQ201 ERDLLKTFRI 211 SSDTFITYMM221 TLEDHYHSDV231 AYHNSLHAAD241 VAQSTHVLLS251 TPALDAVFTD 261 LEILAAIFAA271 AIHDVDHPGV281 SNQFLINTNS291 ELALMYNDES301 VLENHHLAVG 311 FKLLQEEHCD321 IFMNLTKKQR331 QTLRKMVIDM341 VLATDMSKHM351 SLLADLKTMV 361 ETKKVTSSGV371 LLLDNYTDRI381 QVLRNMVHCA391 DLSNPTKSLE401 LYRQWTDRIM 411 EEFFQQGDKE421 RERGMEISPM431 CDKHTASVEK441 SQVGFIDYIV451 HPLWETWADL 461 VQPDAQDILD471 TLEDNRNWYQ481 SMIPQAPAPP491 LDEQ
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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 .ROL or .ROL2 or .ROL3 or :3ROL;style chemicals stick;color identity;select .A:233 or .A:234 or .A:238 or .A:275 or .A:345 or .A:347 or .A:392 or .A:393 or .A:395 or .A:396 or .A:403 or .A:406 or .A:407 or .A:410 or .A:411 or .A:414 or .A:431 or .A:439 or .A:442 or .A:443 or .A:446; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
TYR233
2.641
HIS234
2.767
HIS238
3.967
ASP275
4.105
THR345
4.627
MET347
3.454
ASP392
2.645
LEU393
2.656
ASN395
2.477
PRO396
4.280
TYR403
3.405
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| References | Top | ||||
|---|---|---|---|---|---|
| REF 1 | Engineered stabilization and structural analysis of the autoinhibited conformation of PDE4. Proc Natl Acad Sci U S A. 2015 Mar 24;112(12):E1414-22. | ||||
| REF 2 | Structural basis for the activity of drugs that inhibit phosphodiesterases. Structure. 2004 Dec;12(12):2233-47. | ||||
| REF 3 | Crystal structures of the catalytic domain of phosphodiesterase 4B complexed with AMP, 8-Br-AMP, and rolipram. J Mol Biol. 2004 Mar 19;337(2):355-65. | ||||
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