Target Binding Site Detail
| Target General Information | Top | ||||
|---|---|---|---|---|---|
| Target ID | T67619 | Target Info | |||
| Target Name | RAC-alpha serine/threonine-protein kinase (AKT1) | ||||
| Synonyms | RAC-PK-alpha; RAC; Proto-oncogene c-Akt; Protein kinase B alpha; PKB alpha | ||||
| Target Type | Successful Target | ||||
| Gene Name | AKT1 | ||||
| Biochemical Class | Kinase | ||||
| UniProt ID | |||||
| Ligand General Information | Top | ||||
|---|---|---|---|---|---|
| Ligand Name | Phosphonothreonine | Ligand Info | |||
| Canonical SMILES | CC(C(C(=O)O)N)OP(=O)(O)O | ||||
| InChI | 1S/C4H10NO6P/c1-2(3(5)4(6)7)11-12(8,9)10/h2-3H,5H2,1H3,(H,6,7)(H2,8,9,10)/t2-,3+/m1/s1 | ||||
| InChIKey | USRGIUJOYOXOQJ-GBXIJSLDSA-N | ||||
| PubChem Compound ID | 3246323 | ||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| PDB ID: 3CQW Crystal Structure of Akt-1 complexed with substrate peptide and inhibitor | ||||||
| Method | X-ray diffraction | Resolution | 2.00 Å | Mutation | Yes | [1] |
| PDB Sequence |
RVTMNEFEYL
153 KLLGKGTFGK163 VILVKEKATG173 RYYAMKILKK183 EVIVAKDEVA193 HTLTENRVLQ 203 NSRHPFLTAL213 KYSFQTHDRL223 CFVMEYANGG233 ELFFHLSRER243 VFSEDRARFY 253 GAEIVSALDY263 LHSEKNVVYR273 DLKLENLMLD283 KDGHIKITDF293 GLCKEGIKDG 303 ATMKFCGTPE314 YLAPEVLEDN324 DYGRAVDWWG334 LGVVMYEMMC344 GRLPFYNQDH 354 EKLFELILME364 EIRFPRTLGP374 EAKSLLSGLL384 KKDPKQRLGG394 GSEDAKEIMQ 404 HRFFAGIVWQ414 HVYEKKLSPP424 FKPQVTSETD434 TRYFDEEFTA444 QMIERRPHFP 470 QFDYSASS
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| PDB ID: 3MVH Crystal structure of Akt-1-inhibitor complexes | ||||||
| Method | X-ray diffraction | Resolution | 2.01 Å | Mutation | Yes | [2] |
| PDB Sequence |
VTMNEFEYLK
154 LLGKGTFGKV164 ILVKEKATGR174 YYAMKILKKE184 VIVAKDEVAH194 TLTENRVLQN 204 SRHPFLTALK214 YSFQTHDRLC224 FVMEYANGGE234 LFFHLSRERV244 FSEDRARFYG 254 AEIVSALDYL264 HSEKNVVYRD274 LKLENLMLDK284 DGHIKITDFG294 LCKEGIKDGA 304 TMKFCGTPEY315 LAPEVLEDND325 YGRAVDWWGL335 GVVMYEMMCG345 RLPFYNQDHE 355 KLFELILMEE365 IRFPRTLGPE375 AKSLLSGLLK385 KDPKQRLGGG395 SEDAKEIMQH 405 RFFAGIVWQH415 VYEKKLSPPF425 KPQVTSETDT435 RYFDEEFTAQ445 RPHFPQFDYS 475 A
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| PDB ID: 3CQU Crystal Structure of Akt-1 complexed with substrate peptide and inhibitor | ||||||
| Method | X-ray diffraction | Resolution | 2.20 Å | Mutation | Yes | [1] |
| PDB Sequence |
RVTMNEFEYL
153 KLLGKGTFGK163 VILVKEKATG173 RYYAMKILKK183 EVIVAKDEVA193 HTLTENRVLQ 203 NSRHPFLTAL213 KYSFQTHDRL223 CFVMEYANGG233 ELFFHLSRER243 VFSEDRARFY 253 GAEIVSALDY263 LHSEKNVVYR273 DLKLENLMLD283 KDGHIKITDF293 GLCKEGIKDG 303 ATMKFCGTPE314 YLAPEVLEDN324 DYGRAVDWWG334 LGVVMYEMMC344 GRLPFYNQDH 354 EKLFELILME364 EIRFPRTLGP374 EAKSLLSGLL384 KKDPKQRLGG394 GSEDAKEIMQ 404 HRFFAGIVWQ414 HVYEKKLSPP424 FKPQVTSETD434 TRYFDEEFTA444 QMSERRPHFP 470 QFDYSASS
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| PDB ID: 3MV5 Crystal structure of Akt-1-inhibitor complexes | ||||||
| Method | X-ray diffraction | Resolution | 2.47 Å | Mutation | Yes | [2] |
| PDB Sequence |
RVTMNEFEYL
153 KLLGKGTFGK163 VILVKEKATG173 RYYAMKILKK183 EVIVAKDEVA193 HTLTENRVLQ 203 NSRHPFLTAL213 KYSFQTHDRL223 CFVMEYANGG233 ELFFHLSRER243 VFSEDRARFY 253 GAEIVSALDY263 LHSEKNVVYR273 DLKLENLMLD283 KDGHIKITDF293 GLCKEGIKDG 303 ATMKFCGTPE314 YLAPEVLEDN324 DYGRAVDWWG334 LGVVMYEMMC344 GRLPFYNQDH 354 EKLFELILME364 EIRFPRTLGP374 EAKSLLSGLL384 KKDPKQRLGG394 GSEDAKEIMQ 404 HRFFAGIVWQ414 HVYEKKLSPP424 FKPQVTSETD434 TRYFDEEFTA444 QMIRPHFPQF 472 DYSAS
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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 .TPO or .TPO2 or .TPO3 or :3TPO;style chemicals stick;color identity;select .A:273 or .A:297 or .A:306 or .A:307 or .A:309 or .A:310 or .A:326; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| PDB ID: 3QKL Spirochromane Akt Inhibitors | ||||||
| Method | X-ray diffraction | Resolution | 1.90 Å | Mutation | Yes | [3] |
| PDB Sequence |
RVTMNEFEYL
153 KLLGKGTFGK163 VILVKEKATG173 RYYAMKILKK183 EVIVAKDEVA193 HTLTENRVLQ 203 NSRHPFLTAL213 KYSFQTHDRL223 CFVMEYANGG233 ELFFHLSRER243 VFSEDRARFY 253 GAEIVSALDY263 LHSEKNVVYR273 DLKLENLMLD283 KDGHIKITDF293 GLCKEGIKDG 303 ATMKFCGTPE314 YLAPEVLEDN324 DYGRAVDWWG334 LGVVMYEMMC344 GRLPFYNQDH 354 EKLFELILME364 EIRFPRTLGP374 EAKSLLSGLL384 KKDPKQRLGG394 GSEDAKEIMQ 404 HRFFAGIVWQ414 HVYEKKLSPP424 FKPQVTSETD434 TRYFDEEFTA444 QMITRPHFPQ 471 FDYSASS
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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 .TPO or .TPO2 or .TPO3 or :3TPO;style chemicals stick;color identity;select .A:273 or .A:297 or .A:306 or .A:307 or .A:309 or .A:310 or .A:320 or .A:326; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| PDB ID: 4EKL Akt1 with GDC0068 | ||||||
| Method | X-ray diffraction | Resolution | 2.00 Å | Mutation | Yes | [4] |
| PDB Sequence |
RVTMNEFEYL
153 KLLGKGTFGK163 VILVKEKATG173 RYYAMKILKK183 EVIVAKDEVA193 HTLTENRVLQ 203 NSRHPFLTAL213 KYSFQTHDRL223 CFVMEYANGG233 ELFFHLSRER243 VFSEDRARFY 253 GAEIVSALDY263 LHSEKNVVYR273 DLKLENLMLD283 KDGHIKITDF293 GLCKEGIKDG 303 ATMKFCGTPE314 YLAPEVLEDN324 DYGRAVDWWG334 LGVVMYEMMC344 GRLPFYNQDH 354 EKLFELILME364 EIRFPRTLGP374 EAKSLLSGLL384 KKDPKQRLGG394 GSEDAKEIMQ 404 HRFFAGIVWQ414 HVYEKKLSPP424 FKPQVTSETD434 TRYFDEEFTA444 QMITITPSME 459 CVDSERRPHF469 PQFDYSASS
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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 .TPO or .TPO2 or .TPO3 or :3TPO;style chemicals stick;color identity;select .A:273 or .A:297 or .A:306 or .A:307 or .A:309 or .A:310 or .A:320 or .A:326; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| PDB ID: 3QKM Spirocyclic sulfonamides as AKT inhibitors | ||||||
| Method | X-ray diffraction | Resolution | 2.20 Å | Mutation | Yes | [5] |
| PDB Sequence |
RVTMNEFEYL
153 KLLGKGTFGK163 VILVKEKATG173 RYYAMKILKK183 EVIVAKDEVA193 HTLTENRVLQ 203 NSRHPFLTAL213 KYSFQTHDRL223 CFVMEYANGG233 ELFFHLSRER243 VFSEDRARFY 253 GAEIVSALDY263 LHSEKNVVYR273 DLKLENLMLD283 KDGHIKITDF293 GLCKEGIKDG 303 ATMKFCGTPE314 YLAPEVLEDN324 DYGRAVDWWG334 LGVVMYEMMC344 GRLPFYNQDH 354 EKLFELILME364 EIRFPRTLGP374 EAKSLLSGLL384 KKDPKQRLGG394 GSEDAKEIMQ 404 HRFFAGIVWQ414 HVYEKKLSPP424 FKPQVTSETD434 TRYFDEEFTA444 QMITITPSME 459 CVDSERRPHF469 PQFDYSASS
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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 .TPO or .TPO2 or .TPO3 or :3TPO;style chemicals stick;color identity;select .A:194 or .A:273 or .A:297 or .A:306 or .A:307 or .A:309 or .A:310 or .A:320 or .A:326; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| PDB ID: 3QKK Spirochromane Akt Inhibitors | ||||||
| Method | X-ray diffraction | Resolution | 2.30 Å | Mutation | Yes | [3] |
| PDB Sequence |
RVTMNEFEYL
153 KLLGKGTFGK163 VILVKEKATG173 RYYAMKILKK183 EVIVAKDEVA193 HTLTENRVLQ 203 NSRHPFLTAL213 KYSFQTHDRL223 CFVMEYANGG233 ELFFHLSRER243 VFSEDRARFY 253 GAEIVSALDY263 LHSEKNVVYR273 DLKLENLMLD283 KDGHIKITDF293 GLCKEGIKDG 303 ATMKFCGTPE314 YLAPEVLEDN324 DYGRAVDWWG334 LGVVMYEMMC344 GRLPFYNQDH 354 EKLFELILME364 EIRFPRTLGP374 EAKSLLSGLL384 KKDPKQRLGG394 GSEDAKEIMQ 404 HRFFAGIVWQ414 HVYEKKLSPP424 FKPQVTSETD434 TRYFDEEFTA444 QMITIMECVD 462 SERRPHFPQF472 DYSASS
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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 .TPO or .TPO2 or .TPO3 or :3TPO;style chemicals stick;color identity;select .A:273 or .A:297 or .A:306 or .A:307 or .A:309 or .A:310 or .A:320 or .A:326; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| PDB ID: 3OW4 Discovery of dihydrothieno- and dihydrofuropyrimidines as potent pan Akt inhibitors | ||||||
| Method | X-ray diffraction | Resolution | 2.60 Å | Mutation | Yes | [6] |
| PDB Sequence |
RVTMNEFEYL
153 KLLGKGTFGK163 VILVKEKATG173 RYYAMKILKK183 EVIVAKDEVA193 HTLTENRVLQ 203 NSRHPFLTAL213 KYSFQTHDRL223 CFVMEYANGG233 ELFFHLSRER243 VFSEDRARFY 253 GAEIVSALDY263 LHSEKNVVYR273 DLKLENLMLD283 KDGHIKITDF293 GLCKEGIKDG 303 ATMKFCGTPE314 YLAPEVLEDN324 DYGRAVDWWG334 LGVVMYEMMC344 GRLPFYNQDH 354 EKLFELILME364 EIRFPRTLGP374 EAKSLLSGLL384 KKDPKQRLGG394 GSEDAKEIMQ 404 HRFFAGIVWQ414 HVYEKKLSPP424 FKPQVTSETD434 TRYFDEEFTA444 QMITRPHFPQ 471 FDYSASS
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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 .TPO or .TPO2 or .TPO3 or :3TPO;style chemicals stick;color identity;select .A:273 or .A:297 or .A:306 or .A:307 or .A:309 or .A:310 or .A:320 or .A:326; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| PDB ID: 3OCB Akt1 kinase domain with pyrrolopyrimidine inhibitor | ||||||
| Method | X-ray diffraction | Resolution | 2.70 Å | Mutation | Yes | [7] |
| PDB Sequence |
RVTMNEFEYL
153 KLLGKGTFGK163 VILVKEKATG173 RYYAMKILKK183 EVIVAKDEVA193 HTLTENRVLQ 203 NSRHPFLTAL213 KYSFQTHDRL223 CFVMEYANGG233 ELFFHLSRER243 VFSEDRARFY 253 GAEIVSALDY263 LHSEKNVVYR273 DLKLENLMLD283 KDGHIKITDF293 GLCKEGIKDG 303 ATMKFCGTPE314 YLAPEVLEDN324 DYGRAVDWWG334 LGVVMYEMMC344 GRLPFYNQDH 354 EKLFELILME364 EIRFPRTLGP374 EAKSLLSGLL384 KKDPKQRLGG394 GSEDAKEIMQ 404 HRFFAGIVWQ414 HVYEKKLSPP424 FKPQVTSETD434 TRYFDEEFTA444 QMRPHFPQFD 473 YSASS
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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 .TPO or .TPO2 or .TPO3 or :3TPO;style chemicals stick;color identity;select .A:273 or .A:297 or .A:306 or .A:307 or .A:309 or .A:310 or .A:320 or .A:326; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
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| PDB ID: 4EKK Akt1 with AMP-PNP | ||||||
| Method | X-ray diffraction | Resolution | 2.80 Å | Mutation | Yes | [4] |
| PDB Sequence |
RVTMNEFEYL
153 KLLGKGTFGK163 VILVKEKATG173 RYYAMKILKK183 EVIVAKDEVA193 HTLTENRVLQ 203 NSRHPFLTAL213 KYSFQTHDRL223 CFVMEYANGG233 ELFFHLSRER243 VFSEDRARFY 253 GAEIVSALDY263 LHSEKNVVYR273 DLKLENLMLD283 KDGHIKITDF293 GLCKEGIKDG 303 ATMKFCGTPE314 YLAPEVLEDN324 DYGRAVDWWG334 LGVVMYEMMC344 GRLPFYNQDH 354 EKLFELILME364 EIRFPRTLGP374 EAKSLLSGLL384 KKDPKQRLGG394 GSEDAKEIMQ 404 HRFFAGIVWQ414 HVYEKKLSPP424 FKPQVTSETD434 TRYFDEEFTA444 QMISERRPHF 469 PQFDYSAS
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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 .TPO or .TPO2 or .TPO3 or :3TPO;style chemicals stick;color identity;select .A:273 or .A:297 or .A:306 or .A:307 or .A:309 or .A:310 or .A:320 or .A:326; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| PDB ID: 4GV1 PKB alpha in complex with AZD5363 | ||||||
| Method | X-ray diffraction | Resolution | 1.49 Å | Mutation | No | [8] |
| PDB Sequence |
SRVTMNEFEY
152 LKLLGKGTFG162 KVILVKEKAT172 GRYYAMKILK182 KEVIVAKDEV192 AHTLTENRVL 202 QNSRHPFLTA212 LKYSFQTHDR222 LCFVMEYANG232 GELFFHLSRE242 RVFSEDRARF 252 YGAEIVSALD262 YLHSEKNVVY272 RDLKLENLML282 DKDGHIKITD292 FGLCKEGIKD 302 GATMKFCGTP313 EYLAPEVLED323 NDYGRAVDWW333 GLGVVMYEMM343 CGRLPFYNQD 353 HEKLFELILM363 EEIRFPRTLG373 PEAKSLLSGL383 LKKDPKQRLG393 GGSEDAKEIM 403 QHRFFAGIVW413 QHVYEKKLSP423 PFKPQVTSET433 DTRYFDEEFT443 AQMITITPSM 458 ECVDSERRPH468 FPQFDYSAS
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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 .TPO or .TPO2 or .TPO3 or :3TPO;style chemicals stick;color identity;select .A:273 or .A:297 or .A:306 or .A:307 or .A:309 or .A:310 or .A:320 or .A:326; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| References | Top | ||||
|---|---|---|---|---|---|
| REF 1 | Synthesis and structure based optimization of novel Akt inhibitors. Bioorg Med Chem Lett. 2008 Jun 1;18(11):3359-63. | ||||
| REF 2 | Design of selective, ATP-competitive inhibitors of Akt. J Med Chem. 2010 Jun 24;53(12):4615-22. | ||||
| REF 3 | Discovery and SAR of spirochromane Akt inhibitors. Bioorg Med Chem Lett. 2011 Apr 15;21(8):2410-4. | ||||
| REF 4 | An ATP-site on-off switch that restricts phosphatase accessibility of Akt. Sci Signal. 2012 May 8;5(223):ra37. | ||||
| REF 5 | Discovery of spirocyclic sulfonamides as potent Akt inhibitors with exquisite selectivity against PKA. Bioorg Med Chem Lett. 2011 Apr 15;21(8):2335-40. | ||||
| REF 6 | Discovery of dihydrothieno- and dihydrofuropyrimidines as potent pan Akt inhibitors. Bioorg Med Chem Lett. 2010 Dec 1;20(23):7037-41. | ||||
| REF 7 | Discovery of pyrrolopyrimidine inhibitors of Akt. Bioorg Med Chem Lett. 2010 Oct 1;20(19):5607-12. | ||||
| REF 8 | Discovery of 4-amino-N-[(1S)-1-(4-chlorophenyl)-3-hydroxypropyl]-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carboxamide (AZD5363), an orally bioavailable, potent inhibitor of Akt kinases. J Med Chem. 2013 Mar 14;56(5):2059-73. | ||||
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