Target Binding Site Detail
| Target General Information | Top | ||||
|---|---|---|---|---|---|
| Target ID | T37961 | Target Info | |||
| Target Name | PAK-1 protein kinase (PAK1) | ||||
| Synonyms | p65-PAK; p21-activated kinase 1; Serine/threonine-protein kinase PAK 1; PAK-1; Alpha-PAK | ||||
| Target Type | Literature-reported Target | ||||
| Gene Name | PAK1 | ||||
| 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: 3Q53 Structure of phosphorylated PAK1 kinase domain in complex with ATP | ||||||
| Method | X-ray diffraction | Resolution | 2.09 Å | Mutation | Yes | [1] |
| PDB Sequence |
DEEILEKLRS
259 IVSVGDPKKK269 YTRFEKIGQG279 ASGTVYTAMD289 VATGQEVAIR299 QMNLQQQPKK 309 ELIINEILVM319 RENKNPNIVN329 YLDSYLVGDE339 LWVVMEYLAG349 GSLTDVVTET 359 CMDEGQIAAV369 CRECLQALEF379 LHSNQVIHRD389 IKSDNILLGM399 DGSVKLTDFG 409 FCAQITPEQS419 KRSMVGTPYW430 MAPEVVTRKA440 YGPKVDIWSL450 GIMAIEMIEG 460 EPPYLNENPL470 RALYLIATNG480 TPELQNPEKL490 SAIFRDFLNR500 CLEMDVEKRG 510 SAKELIQHQF520 LKIAKPLSSL530 TPLIAAAKEA540 T
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| PDB ID: 4EQC Crystal structure of PAK1 kinase domain in complex with FRAX597 inhibitor | ||||||
| Method | X-ray diffraction | Resolution | 2.01 Å | Mutation | Yes | [2] |
| PDB Sequence |
DPFTSDEEIL
254 EKLRSIVSVG264 DPKKKYTRFE274 KIGQGASGTV284 YTAMDVATGQ294 EVAIRQMNLQ 304 QQPKKELIIN314 EILVMRENKN324 PNIVNYLDSY334 LVGDELWVVM344 EYLAGGSLTD 354 VVTETCMDEG364 QIAAVCRECL374 QALEFLHSNQ384 VIHRDIKSDN394 ILLGMDGSVK 404 LTDFGFCAQI414 TPEQSKRSMV425 GTPYWMAPEV435 VTRKAYGPKV445 DIWSLGIMAI 455 EMIEGEPPYL465 NENPLRALYL475 IATNGTPELQ485 NPEKLSAIFR495 DFLNRCLEMD 505 VEKRGSAKEL515 LQHQFLKIAK525 PLSSLTPLIA535 AAKEAT
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| PDB ID: 7VTO The crystal structure of PAK1 with the inhibitor GW8510 | ||||||
| Method | X-ray diffraction | Resolution | 2.59 Å | Mutation | No | [3] |
| PDB Sequence |
LRSIVKIGQG
279 ASGTVYTAMD289 VATGQEVAIK299 QPKKELIINE315 ILVMRENKNP325 NIVNYLDSYL 340 WVVMEYLAGG350 SLTDVVTETC360 MDEGQIAAVC370 RECLQALEFL380 HSNQVIHRNI 390 KSDNILLGMD400 GSVKLTDFGF410 CAQITPEQSK420 RSMVGTPYWM431 APEVVTRKAY 441 GPKVDIWSLG451 IMAIEMIEGE461 PPYLNENPLR471 ALYLIATNGT481 PELQNPEKLS 491 AIFRDFLNRC501 LEMDVEKRGS511 AKELLQHQFL521 KIAKPLSSLT531 PLIAAAKEAT 541 K
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| PDB ID: 3FXZ Crystal structure of PAK1 kinase domain with ruthenium complex lambda-FL172 | ||||||
| Method | X-ray diffraction | Resolution | 1.64 Å | Mutation | Yes | [4] |
| PDB Sequence |
SDEEILEKLR
258 SIVSVGDPKK268 KYTRFEKIGQ278 GASGTVYTAM288 DVATGQEVAI298 RQMNLQQQPK 308 KELIINEILV318 MRENKNPNIV328 NYLDSYLVGD338 ELWVVMEYLA348 GGSLTDVVTE 358 TCMDEGQIAA368 VCRECLQALE378 FLHSNQVIHR388 DIKSDNILLG398 MDGSVKLTDF 408 GFCAQITPEQ418 SKRSMVGTPY429 WMAPEVVTRK439 AYGPKVDIWS449 LGIMAIEMIE 459 GEPPYLNENP469 LRALYLIATN479 GTPELQNPEK489 LSAIFRDFLN499 RCLEMDVEKR 509 GSAKELLQHQ519 FLKIAKPLSS529 LTPLIAAAKE539 AT
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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:388 or .A:421 or .A:422 or .A:424 or .A:425 or .A:435 or .A:441; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| PDB ID: 4DAW Crystal structure of PAK1 kinase domain with the ruthenium phthalimide complex | ||||||
| Method | X-ray diffraction | Resolution | 2.00 Å | Mutation | Yes | [5] |
| PDB Sequence |
SDEEILEKLR
258 SIVSVGDPKK268 KYTRFEKIGQ278 GASGTVYTAM288 DVATGQEVAI298 RQMNLQQQPK 308 KELIINEILV318 MRENKNPNIV328 NYLDSYLVGD338 ELWVVMEYLA348 GGSLTDVVTE 358 TCMDEGQIAA368 VCRECLQALE378 FLHSNQVIHR388 DIKSDNILLG398 MDGSVKLTDF 408 GFCAQITPEQ418 SKRSMVGTPY429 WMAPEVVTRK439 AYGPKVDIWS449 LGIMAIEMIE 459 GEPPYLNENP469 LRALYLIATN479 GTPELQNPEK489 LSAIFRDFLN499 RCLEMDVEKR 509 GSAKELLQHQ519 FLKIAKPLSS529 LTPLIAAAKE539 ATK
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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:388 or .A:421 or .A:422 or .A:424 or .A:425 or .A:435 or .A:441; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| PDB ID: 5DFP Crystal structure of PAK1 in complex with an inhibitor compound FRAX1036 | ||||||
| Method | X-ray diffraction | Resolution | 2.20 Å | Mutation | Yes | [6] |
| PDB Sequence |
SDEEILEKLR
258 SIVSVGDPKK268 KYTRFEKIGQ278 GASGTVYTAM288 DVATGQEVAI298 RQMNLQQQPK 308 KELIINEILV318 MRENKNPNIV328 NYLDSYLVGD338 ELWVVMEYLA348 GGSLTDVVTE 358 TCMDEGQIAA368 VCRECLQALE378 FLHSNQVIHR388 DIKSDNILLG398 MDGSVKLTDF 408 GFCAQITPEQ418 SKRSMVGTPY429 WMAPEVVTRK439 AYGPKVDIWS449 LGIMAIEMIE 459 GEPPYLNENP469 LRALYLIATN479 GTPELQNPEK489 LSAIFRDFLN499 RCLEMDVEKR 509 GSAKELLQHQ519 FLKIAKPLSS529 LTPLIAAAKE539 AT
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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:388 or .A:421 or .A:422 or .A:424 or .A:425 or .A:435 or .A:441; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| PDB ID: 3FY0 Crystal structure of PAK1 kinase domain with ruthenium complex DW1 | ||||||
| Method | X-ray diffraction | Resolution | 2.35 Å | Mutation | Yes | [4] |
| PDB Sequence |
SDEEILEKLR
258 SIVSVGDPKK268 KYTRFEKIGQ278 GASGTVYTAM288 DVATGQEVAI298 RQMNLQQQPK 308 KELIINEILV318 MRENKNPNIV328 NYLDSYLVGD338 ELWVVMEYLA348 GGSLTDVVTE 358 TCMDEGQIAA368 VCRECLQALE378 FLHSNQVIHR388 DIKSDNILLG398 MDGSVKLTDF 408 GFCAQITPEQ418 SKRSMVGTPY429 WMAPEVVTRK439 AYGPKVDIWS449 LGIMAIEMIE 459 GEPPYLNENP469 LRALYLIATN479 GTPELQNPEK489 LSAIFRDFLN499 RCLEMDVEKR 509 GSAKELLQHQ519 FLKIAKPLSS529 LTPLIAAAKE539 AT
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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:388 or .A:421 or .A:422 or .A:424 or .A:425 or .A:435 or .A:441; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| PDB ID: 4ZLO Serine/threonine-protein kinase PAK1 complexed with a dibenzodiazepine: identification of an allosteric site on PAK1 | ||||||
| Method | X-ray diffraction | Resolution | 2.50 Å | Mutation | No | [7] |
| PDB Sequence |
DEEILEKLRS
259 IVSVGDPKKK269 YTRFEKIGQS281 GTVYTAMDVA291 TGQEVAIKQM301 NKKELIINEI 316 LVMRENKNPN326 IVNYLDSYLV336 GDELWVVMEY346 LAGGSLTDVV356 TETCMDEGQI 366 AAVCRECLQA376 LEFLHSNQVI386 HRDIKSDNIL396 LGMDGSVKLT406 DFGSKRSMVG 426 TPYWMAPEVV436 TRKAYGPKVD446 IWSLGIMAIE456 MIEGEPPYLN466 ENPLRALYLI 476 ATNGTPELQN486 PEKLSAIFRD496 FLNRCLEMDV506 EKRGSAKELL516 QHQFLKIAKP 526 LSSLTPLIAA536 AKEATKN
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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:421 or .A:422 or .A:424 or .A:425; 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 | Structural insights into the autoactivation mechanism of p21-activated protein kinase. Structure. 2011 Dec 7;19(12):1752-61. | ||||
| REF 2 | FRAX597, a small molecule inhibitor of the p21-activated kinases, inhibits tumorigenesis of neurofibromatosis type 2 (NF2)-associated Schwannomas. J Biol Chem. 2013 Oct 4;288(40):29105-14. | ||||
| REF 3 | The crystal structure of PAK1 with the inhibitor GW8510 | ||||
| REF 4 | Targeting large kinase active site with rigid, bulky octahedral ruthenium complexes. J Am Chem Soc. 2008 Nov 26;130(47):15764-5. | ||||
| REF 5 | The art of filling protein pockets efficiently with octahedral metal complexes. Angew Chem Int Ed Engl. 2012 May 21;51(21):5244-6. | ||||
| REF 6 | Design of Selective PAK1 Inhibitor G-5555: Improving Properties by Employing an Unorthodox Low-pK a Polar Moiety. ACS Med Chem Lett. 2015 Oct 31;6(12):1241-6. | ||||
| REF 7 | Optimization of a Dibenzodiazepine Hit to a Potent and Selective Allosteric PAK1 Inhibitor. ACS Med Chem Lett. 2015 May 22;6(7):776-81. | ||||
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