Binding Site Information of Target
| Target General Information | Top | ||||
|---|---|---|---|---|---|
| Target ID | T23995 | Target Info | |||
| Target Name | Protein kinase C theta (PRKCQ) | ||||
| Synonyms | Protein kinase C theta type; PRKCT; NPKC-theta | ||||
| Target Type | Clinical trial Target | ||||
| Gene Name | PRKCQ | ||||
| Biochemical Class | Kinase | ||||
| UniProt ID | |||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| Ligand Name: L-serine-O-phosphate | Ligand Info | |||||
| Structure Description | Crystal Structure of PKC-theta complexed with Staurosporine at 2A resolution | PDB:1XJD | ||||
| Method | X-ray diffraction | Resolution | 2.00 Å | Mutation | Yes | [1] |
| PDB Sequence |
IEDFILHKML
386 GKGSFGKVFL396 AEFKKTNQFF406 AIKALKKDVV416 LMDDDVECTM426 VEKRVLSLAW 436 EHPFLTHMFC446 TFQTKENLFF456 VMEYLNGGDL466 MYHIQSCHKF476 DLSRATFYAA 486 EIILGLQFLH496 SKGIVYRDLK506 LDNILLDKDG516 HIKIADFGMC526 KENMLGDAKT 536 NFCGTPDYIA547 PEILLGQKYN557 HSVDWWSFGV567 LLYEMLIGQS577 PFHGQDEEEL 587 FHSIRMDNPF597 YPRWLEKEAK607 DLLVKLFVRE617 PEKRLGVRGD627 IRQHPLFREI 637 NWEELERKEI647 DPQNMFRNFF696
|
|||||
|
|
||||||
| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Ligand Name: Phosphonothreonine | Ligand Info | |||||
| Structure Description | Crystal Structure of PKC-theta complexed with Staurosporine at 2A resolution | PDB:1XJD | ||||
| Method | X-ray diffraction | Resolution | 2.00 Å | Mutation | Yes | [1] |
| PDB Sequence |
IEDFILHKML
386 GKGSFGKVFL396 AEFKKTNQFF406 AIKALKKDVV416 LMDDDVECTM426 VEKRVLSLAW 436 EHPFLTHMFC446 TFQTKENLFF456 VMEYLNGGDL466 MYHIQSCHKF476 DLSRATFYAA 486 EIILGLQFLH496 SKGIVYRDLK506 LDNILLDKDG516 HIKIADFGMC526 KENMLGDAKT 536 NFCGTPDYIA547 PEILLGQKYN557 HSVDWWSFGV567 LLYEMLIGQS577 PFHGQDEEEL 587 FHSIRMDNPF597 YPRWLEKEAK607 DLLVKLFVRE617 PEKRLGVRGD627 IRQHPLFREI 637 NWEELERKEI647 DPQNMFRNFF696
|
|||||
|
|
||||||
| Ligand Name: Staurosporine | Ligand Info | |||||
| Structure Description | Crystal Structure of PKC-theta complexed with Staurosporine at 2A resolution | PDB:1XJD | ||||
| Method | X-ray diffraction | Resolution | 2.00 Å | Mutation | Yes | [1] |
| PDB Sequence |
IEDFILHKML
386 GKGSFGKVFL396 AEFKKTNQFF406 AIKALKKDVV416 LMDDDVECTM426 VEKRVLSLAW 436 EHPFLTHMFC446 TFQTKENLFF456 VMEYLNGGDL466 MYHIQSCHKF476 DLSRATFYAA 486 EIILGLQFLH496 SKGIVYRDLK506 LDNILLDKDG516 HIKIADFGMC526 KENMLGDAKT 536 NFCGTPDYIA547 PEILLGQKYN557 HSVDWWSFGV567 LLYEMLIGQS577 PFHGQDEEEL 587 FHSIRMDNPF597 YPRWLEKEAK607 DLLVKLFVRE617 PEKRLGVRGD627 IRQHPLFREI 637 NWEELERKEI647 DPQNMFRNFF696
|
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .STU or .STU2 or .STU3 or :3STU;style chemicals stick;color identity;select .A:386 or .A:387 or .A:388 or .A:389 or .A:390 or .A:394 or .A:407 or .A:409 or .A:428 or .A:442 or .A:458 or .A:459 or .A:460 or .A:461 or .A:462 or .A:464 or .A:465 or .A:467 or .A:508 or .A:509 or .A:511 or .A:521 or .A:522; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
LEU386
3.226
GLY387
3.644
LYS388
3.247
GLY389
3.392
SER390
4.824
VAL394
3.677
ALA407
3.207
LYS409
3.414
GLU428
3.853
THR442
4.068
MET458
3.504
GLU459
2.773
|
|||||
| Ligand Name: 2,2-Dimethyl-7-(2-Oxidanylidene-3~{h}-Imidazo[4,5-B]pyridin-1-Yl)-1-(Phenylmethyl)-3~{h}-Quinazolin-4-One | Ligand Info | |||||
| Structure Description | Structure of Protein Kinase C theta with compound 10: 2,2-dimethyl-7-(2-oxidanylidene-3~{H}-imidazo[4,5-b]pyridin-1-yl)-1-(phenylmethyl)-3~{H}-quinazolin-4-one | PDB:5F9E | ||||
| Method | X-ray diffraction | Resolution | 2.00 Å | Mutation | No | [2] |
| PDB Sequence |
KLKIEDFELH
383 KMLGKGSFGK393 VFLAEFKKTN403 QFFAIKALKK413 DVVLMDDDVE423 CTMVEKRVLS 433 LAWEHPFLTH443 MFCTFQTKEN453 LFFVMEYLNG463 GDLMYHIQSC473 HKFDLSRATF 483 YAAEIILGLQ493 FLHSKGIVYR503 DLKLDNILLD513 KDGHIKIADF523 GMCKENMLGD 533 AKTNEFCGTP543 DYIAPEILLG553 QKYNHSVDWW563 SFGVLLYEML573 IGQSPFHGQD 583 EEELFHSIRM593 DNPFYPRWLE603 KEAKDLLVKL613 FVREPEKRLG623 VRGDIRQHPL 633 FREINWEELE643 RKEIDPPFRP653 KVKSPFDCSN663 FDKEFLNEKP673 RLFADRALIN 684 SMDQNMFRNF694 FMNPGMERLI705 SHHH
|
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .5VS or .5VS2 or .5VS3 or :35VS;style chemicals stick;color identity;select .A:386 or .A:387 or .A:391 or .A:394 or .A:407 or .A:409 or .A:428 or .A:442 or .A:458 or .A:459 or .A:460 or .A:461 or .A:465 or .A:508 or .A:509 or .A:511 or .A:521 or .A:522 or .A:664; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
||||||
| Ligand Name: (1r)-9-(Azetidin-3-Ylamino)-1,8-Dimethyl-3,5-Dihydro[1,2,4]triazino[3,4-C][1,4]benzoxazin-2(1h)-One | Ligand Info | |||||
| Structure Description | Human Protein Kinase C Theta in Complex with Compound35 ((1R)-9-(AZETIDIN-3-YLAMINO)-1,8-DIMETHYL-3,5-DIHYDRO[1,2,4]TRIAZINO[3,4-C][1,4]BENZOXAZIN-2(1H)-ONE) | PDB:4Q9Z | ||||
| Method | X-ray diffraction | Resolution | 2.60 Å | Mutation | Yes | [3] |
| PDB Sequence |
LKIEDFELHK
384 MLGKGSFGKV394 FLAEFKKTNQ404 FFAIKALKKD414 VVLMDDDVEC424 TMVEKRVLSL 434 AWEHPFLTHM444 FCTFQTKENL454 FFVMEYLNGG464 DLMYHIQSCH474 KFDLSRATFY 484 AAEIILGLQF494 LHSKGIVYRD504 LKLDNILLDK514 DGHIKIADFG524 MCKENMLGDA 534 KTNEFCGTPD544 YIAPEILLGQ554 KYNHSVDWWS564 FGVLLYEMLI574 GQSPFHGQDE 584 EELFHSIRMD594 NPFYPRWLEK604 EAKDLLVKLF614 VREPEKRLGV624 RGDIRQHPLF 634 REINWEELER644 KEIDPPFRPK654 VKSPFDCSNF664 DKEFLNEKPR674 LFADRALINS 685 MDQNMFRNFF696 MNPGMERLIS706 H
|
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .PZW or .PZW2 or .PZW3 or :3PZW;style chemicals stick;color identity;select .A:386 or .A:387 or .A:391 or .A:394 or .A:407 or .A:409 or .A:442 or .A:458 or .A:459 or .A:460 or .A:461 or .A:508 or .A:509 or .A:511 or .A:521 or .A:522 or .A:664; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
||||||
| Ligand Name: (1r)-9-[(1,3-Dimethylazetidin-3-Yl)(Methyl)amino]-1-Methyl-8-Phenyl-3,5-Dihydro[1,2,4]triazino[3,4-C][1,4]benzoxazin-2(1h)-One | Ligand Info | |||||
| Structure Description | Human Protein Kinase C THETA IN COMPLEX WITH LIGAND COMPOUND 11a (6-[(1,3-Dimethyl-azetidin-3-yl)-methyl-amino]-4(R)-methyl-7-phenyl-2,10-dihydro-9-oxa-1,2,4a-triaza-phenanthren-3-one) | PDB:4RA5 | ||||
| Method | X-ray diffraction | Resolution | 2.61 Å | Mutation | Yes | [4] |
| PDB Sequence |
KLKIEDFELH
383 KMLGKGSFGK393 VFLAEFKKTN403 QFFAIKALKK413 DVVLMDDDVE423 CTMVEKRVLS 433 LAWEHPFLTH443 MFCTFQTKEN453 LFFVMEYLNG463 GDLMYHIQSC473 HKFDLSRATF 483 YAAEIILGLQ493 FLHSKGIVYR503 DLKLDNILLD513 KDGHIKIADF523 GMCKENMLGD 533 AKTNEFCGTP543 DYIAPEILLG553 QKYNHSVDWW563 SFGVLLYEML573 IGQSPFHGQD 583 EEELFHSIRM593 DNPFYPRWLE603 KEAKDLLVKL613 FVREPEKRLG623 VRGDIRQHPL 633 FREINWEELE643 RKEIDPPFRP653 KVKSPFDCSN663 FDKEFLNEKP673 RLFADRALIN 684 SMDQNMFRNF694 FMNPGMERLI705 SH
|
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .3L0 or .3L02 or .3L03 or :33L0;style chemicals stick;color identity;select .A:386 or .A:387 or .A:388 or .A:391 or .A:394 or .A:407 or .A:409 or .A:442 or .A:458 or .A:459 or .A:460 or .A:461 or .A:465 or .A:508 or .A:509 or .A:511 or .A:521 or .A:522 or .A:664 or .A:668; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
LEU386
3.467
GLY387
3.628
LYS388
3.430
PHE391
4.062
VAL394
3.515
ALA407
3.400
LYS409
4.548
THR442
3.706
MET458
3.317
GLU459
2.822
|
|||||
| Ligand Name: 3-(8-DIMETHYLAMINOMETHYL-6,7,8,9-TETRAHYDRO-PYRIDO[1,2-A]INDOL-10-YL)-4-(1-METHYL-1H-INDOL-3-YL)-PYRROLE-2,5-DIONE | Ligand Info | |||||
| Structure Description | The crystal structure of the kinase domain of the protein kinase C theta in complex with NVP-XAA228 at 2.32A resolution. | PDB:2JED | ||||
| Method | X-ray diffraction | Resolution | 2.32 Å | Mutation | Yes | [5] |
| PDB Sequence |
LKIEDFELHK
384 MLGKGSFGKV394 FLAEFKKTNQ404 FFAIKALKKD414 VVLMDDDVEC424 TMVEKRVLSL 434 AWEHPFLTHM444 FCTFQTKENL454 FFVMEYLNGG464 DLMYHIQSCH474 KFDLSRATFY 484 AAEIILGLQF494 LHSKGIVYRD504 LKLDNILLDK514 DGHIKIADFG524 MCKENMLGDA 534 KTNEFCGTPD544 YIAPEILLGQ554 KYNHSVDWWS564 FGVLLYEMLI574 GQSPFHGQDE 584 EELFHSIRMD594 NPFYPRWLEK604 EAKDLLVKLF614 VREPEKRLGV624 RGDIRQHPLF 634 REINWEELER644 KEIDPPFRPK654 VKSPFDCSNF664 DKEFLNEKPR674 LFADRALINS 685 MDQNMFRNFF696 MNPG
|
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .LG8 or .LG82 or .LG83 or :3LG8;style chemicals stick;color identity;select .A:386 or .A:387 or .A:391 or .A:394 or .A:407 or .A:409 or .A:428 or .A:442 or .A:458 or .A:459 or .A:460 or .A:461 or .A:465 or .A:508 or .A:509 or .A:511 or .A:521 or .A:522 or .A:664; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
||||||
| References | Top | ||||
|---|---|---|---|---|---|
| REF 1 | Catalytic domain crystal structure of protein kinase C-theta (PKCtheta). J Biol Chem. 2004 Nov 26;279(48):50401-9. | ||||
| REF 2 | Discovery and optimization of 1,7-disubstituted-2,2-dimethyl-2,3-dihydroquinazolin-4(1H)-ones as potent and selective PKC-Theta inhibitors. Bioorg Med Chem. 2016 Jun 1;24(11):2466-75. | ||||
| REF 3 | Discovery of selective and orally bioavailable protein kinase C (PKC) inhibitors from a fragment hit. J Med Chem. 2015 Jan 8;58(1):222-36. | ||||
| REF 4 | Optimized protein kinase C-Theta (PKC-Theta) inhibitors reveal only modest anti-inflammatory efficacy in a rodent model of arthritis. J Med Chem. 2015 Jan 8;58(1):333-46. | ||||
| REF 5 | The Crystal Structure of the Kinase Domain of the Protein Kinase C Theta in Complex with Nvp-Xaa228 | ||||
If You Find Any Error in Data or Bug in Web Service, Please Kindly Report It to Dr. Zhou and Dr. Zhang.