Binding Site Information of Target
| Target General Information | Top | ||||
|---|---|---|---|---|---|
| Target ID | T97821 | Target Info | |||
| Target Name | MLK-related kinase (MLTK) | ||||
| Synonyms | ZAK; Sterile alpha motif- and leucine zipper-containing kinase AZK; Mixed lineage kinase-related kinase; Mitogen-activated protein kinase kinase kinase MLT; Mitogen-activated protein kinase kinase kinase 20; MRK; MLTK; MLK-like mitogen-activated protein triple kinase; Leucine zipper- and sterile alpha motif-containing kinase; Human cervical cancer suppressor gene 4 protein; HCCS4; HCCS-4 | ||||
| Target Type | Literature-reported Target | ||||
| Gene Name | MAP3K20 | ||||
| UniProt ID | |||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| Ligand Name: Vemurafenib | Ligand Info | |||||
| Structure Description | Human leucine zipper- and sterile alpha motif-containing kinase (ZAK, MLT, HCCS-4, MRK, AZK, MLTK) in complex with vemurafenib | PDB:5HES | ||||
| Method | X-ray diffraction | Resolution | 2.14 Å | Mutation | No | [1] |
| PDB Sequence |
ASFVQIKFDD
15 LQFFENCGGG25 SFGSVYRAKW35 ISQDKEVAVK45 KLLKIEKEAE55 ILSVLSHRNI 65 IQFYGVILEP75 PNYGIVTEYA85 SLGSLYDYIN95 SNRSEEMDMD105 HIMTWATDVA 115 KGMHYLHMEA125 PVKVIHRDLK135 SRNVVIAADG145 VLKICDFGAS155 RFHNHGTFPW 172 MAPEVIQSLP182 VSETCDTYSY192 GVVLWEMLTR202 EVPFKGLEGL212 QVAWLVVEKN 222 ERLTIPSSCP232 RSFAELLHQC242 WEADAKKRPS252 FKQIISILES262 MSNDTSLPDK 272 CNSFLHNKAE282 WRCEIEATLE292 RLKKLER
|
|||||
|
|
CYS22
4.039
GLY23
3.513
PHE27
3.629
VAL30
3.518
ALA43
3.257
VAL44
3.831
LYS45
3.530
LEU57
4.185
ILE66
3.663
GLN67
4.535
PHE68
3.982
ILE80
3.598
THR82
3.224
|
|||||
| Ligand Name: Phosphonothreonine | Ligand Info | |||||
| Structure Description | Human leucine zipper- and sterile alpha motif-containing kinase (ZAK, MLT, HCCS-4, MRK, AZK, MLTK) in complex with vemurafenib | PDB:5HES | ||||
| Method | X-ray diffraction | Resolution | 2.14 Å | Mutation | No | [1] |
| PDB Sequence |
ASFVQIKFDD
15 LQFFENCGGG25 SFGSVYRAKW35 ISQDKEVAVK45 KLLKIEKEAE55 ILSVLSHRNI 65 IQFYGVILEP75 PNYGIVTEYA85 SLGSLYDYIN95 SNRSEEMDMD105 HIMTWATDVA 115 KGMHYLHMEA125 PVKVIHRDLK135 SRNVVIAADG145 VLKICDFGAS155 RFHNHGTFPW 172 MAPEVIQSLP182 VSETCDTYSY192 GVVLWEMLTR202 EVPFKGLEGL212 QVAWLVVEKN 222 ERLTIPSSCP232 RSFAELLHQC242 WEADAKKRPS252 FKQIISILES262 MSNDTSLPDK 272 CNSFLHNKAE282 WRCEIEATLE292 RLKKLER
|
|||||
|
|
||||||
| Ligand Name: N-[2,4-bis(fluoranyl)-3-[2-(3-methoxy-1H-pyrazolo[3,4-b]pyridin-5-yl)ethynyl]phenyl]-3-bromanyl-benzenesulfonamide | Ligand Info | |||||
| Structure Description | Crystal structure of ZAK in complex with compound D2829 | PDB:5X5O | ||||
| Method | X-ray diffraction | Resolution | 1.87 Å | Mutation | No | [2] |
| PDB Sequence |
FVQIKFDDLQ
17 FFENCGGGSF27 GSVYRAKWIS37 QDKEVAVKKL47 LKIEKEAEIL57 SVLSHRNIIQ 67 FYGVILEPPN77 YGIVTEYASL87 GSLYDYINSN97 RSEEMDMDHI107 MTWATDVAKG 117 MHYLHMEAPV127 KVIHRDLKSR137 NVVIAADGVL147 KICDFGASRF157 HNHTTHSLVG 168 TFPWMAPEVI178 QSLPVSETCD188 TYSYGVVLWE198 MLTREVPFKG208 LEGLQVAWLV 218 VEKNERLTIP228 SSCPRSFAEL238 LHQCWEADAK248 KRPSFKQIIS258 ILESMSNDTS 268 LPDKCNSFLH278 NKAEWRCEIE288 ATLERLKKLE298 R
|
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .7Z0 or .7Z02 or .7Z03 or :37Z0;style chemicals stick;color identity;select .A:8 or .A:30 or .A:43 or .A:44 or .A:45 or .A:54 or .A:57 or .A:58 or .A:66 or .A:68 or .A:80 or .A:81 or .A:82 or .A:83 or .A:84 or .A:85 or .A:88 or .A:89 or .A:92 or .A:140 or .A:150 or .A:151 or .A:152 or .A:153 or .A:154 or .A:158; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
PHE8
4.838
VAL30
3.914
ALA43
3.279
VAL44
3.563
LYS45
3.342
ALA54
3.841
LEU57
3.739
SER58
4.415
ILE66
3.579
PHE68
3.671
ILE80
3.523
VAL81
4.875
THR82
3.471
|
|||||
| Ligand Name: N-[2,4-difluoro-3-[4-(3-methoxy-1H-pyrazolo[3,4-b]pyridin-5-yl)triazol-1-yl]phenyl]naphthalene-1-sulfonamide | Ligand Info | |||||
| Structure Description | Crystal structure of ZAK in complex with compound 6r | PDB:6JUU | ||||
| Method | X-ray diffraction | Resolution | 1.90 Å | Mutation | No | [3] |
| PDB Sequence |
FVQIKFDDLQ
17 FFENCGGGSF27 GSVYRAKWIS37 QDKEVAVKKL47 LKIEKEAEIL57 SVLSHRNIIQ 67 FYGVILEPPN77 YGIVTEYASL87 GSLYDYINSN97 RSEEMDMDHI107 MTWATDVAKG 117 MHYLHMEAPV127 KVIHRDLKSR137 NVVIAADGVL147 KICDFGASRF157 HNHTTHMSLV 167 GTFPWMAPEV177 IQSLPVSETC187 DTYSYGVVLW197 EMLTREVPFK207 GLEGLQVAWL 217 VVEKNERLTI227 PSSCPRSFAE237 LLHQCWEADA247 KKRPSFKQII257 SILESMSNDT 267 SLPDKCNSFL277 HNKAEWRCEI287 EATLERLKKL297 ER
|
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .C9R or .C9R2 or .C9R3 or :3C9R;style chemicals stick;color identity;select .A:30 or .A:43 or .A:44 or .A:45 or .A:54 or .A:57 or .A:58 or .A:66 or .A:68 or .A:80 or .A:81 or .A:82 or .A:83 or .A:84 or .A:85 or .A:86 or .A:88 or .A:89 or .A:92 or .A:140 or .A:150 or .A:151 or .A:152 or .A:153 or .A:154 or .A:157 or .A:158; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
VAL30
3.448
ALA43
3.399
VAL44
3.822
LYS45
3.442
ALA54
3.465
LEU57
3.467
SER58
4.224
ILE66
3.888
PHE68
3.600
ILE80
3.441
VAL81
4.723
THR82
3.310
GLU83
3.821
TYR84
3.246
|
|||||
| Ligand Name: 3-bromo-N-[2,4-difluoro-3-[4-(3-methoxy-1H-pyrazolo[3,4-b]pyridin-5-yl)triazol-1-yl]phenyl]benzenesulfonamide | Ligand Info | |||||
| Structure Description | Crystal structure of ZAK in complex with compound 6k | PDB:6JUT | ||||
| Method | X-ray diffraction | Resolution | 2.10 Å | Mutation | No | [3] |
| PDB Sequence |
FVQIKFDDLQ
17 FFENCGGGSF27 GSVYRAKWIS37 QDKEVAVKKL47 LKIEKEAEIL57 SVLSHRNIIQ 67 FYGVILEPPN77 YGIVTEYASL87 GSLYDYINSN97 RSEEMDMDHI107 MTWATDVAKG 117 MHYLHMEAPV127 KVIHRDLKSR137 NVVIAADGVL147 KICDFGASRF157 HNHTTHMSLV 167 GTFPWMAPEV177 IQSLPVSETC187 DTYSYGVVLW197 EMLTREVPFK207 GLEGLQVAWL 217 VVEKNERLTI227 PSSCPRSFAE237 LLHQCWEADA247 KKRPSFKQII257 SILESMSNDT 267 SLPDKCNSFL277 HNKAEWRCEI287 EATLERLKKL297 ERDLSFK
|
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .C9O or .C9O2 or .C9O3 or :3C9O;style chemicals stick;color identity;select .A:22 or .A:30 or .A:43 or .A:44 or .A:45 or .A:53 or .A:54 or .A:57 or .A:58 or .A:66 or .A:68 or .A:80 or .A:81 or .A:82 or .A:83 or .A:84 or .A:85 or .A:86 or .A:88 or .A:89 or .A:140 or .A:150 or .A:151 or .A:152 or .A:153 or .A:154 or .A:157; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
CYS22
3.353
VAL30
3.502
ALA43
3.501
VAL44
3.771
LYS45
3.367
GLU53
4.862
ALA54
3.023
LEU57
3.913
SER58
3.674
ILE66
3.749
PHE68
3.643
ILE80
3.549
VAL81
4.986
THR82
3.428
|
|||||
| References | Top | ||||
|---|---|---|---|---|---|
| REF 1 | Structure of the Human Protein Kinase ZAK in Complex with Vemurafenib. ACS Chem Biol. 2016 Jun 17;11(6):1595-602. | ||||
| REF 2 | Structure Based Design of N-(3-((1H-Pyrazolo[3,4-b]pyridin-5-yl)ethynyl)benzenesulfonamides as Selective Leucine-Zipper and Sterile-Alpha Motif Kinase (ZAK) Inhibitors. J Med Chem. 2017 Jul 13;60(13):5927-5932. | ||||
| REF 3 | Design, Synthesis, and Structure-Activity Relationships of 1,2,3-Triazole Benzenesulfonamides as New Selective Leucine-Zipper and Sterile-Alpha Motif Kinase (ZAK) Inhibitors. J Med Chem. 2020 Mar 12;63(5):2114-2130. | ||||
If You Find Any Error in Data or Bug in Web Service, Please Kindly Report It to Dr. Zhou and Dr. Zhang.