Target Binding Site Detail
| Target General Information | Top | ||||
|---|---|---|---|---|---|
| Target ID | T65864 | Target Info | |||
| Target Name | Stress-activated protein kinase 2a (p38 alpha) | ||||
| Synonyms | SAPK2A; P38 mitogen activatedprotein kinase; P38 Mitogen-activatedprotein kinase alpha; Mitogen-activated protein kinase p38 alpha; Mitogen-activated protein kinase 14; MXI2; MAX-interacting protein 2; MAPK 14; MAP kinase p38alpha; MAP kinase p38 alpha; MAP kinase MXI2; MAP kinase 14; Cytokine suppressive anti-inflammatory drug-binding protein; Cytokine suppressive anti-inflammatory drug binding protein; CSPB1; CSBP2; CSBP1; CSBP; CSAID-binding protein; CSAID binding protein; CRK1 | ||||
| Target Type | Clinical trial Target | ||||
| Gene Name | MAPK14 | ||||
| Biochemical Class | Kinase | ||||
| UniProt ID | |||||
| Ligand General Information | Top | ||||
|---|---|---|---|---|---|
| Ligand Name | 4-[5-(4-Fluoro-phenyl)-2-(4-methanesulfinyl-phenyl)-3H-imidazol-4-YL]-pyridine | Ligand Info | |||
| Canonical SMILES | CS(=O)C1=CC=C(C=C1)C2=NC(=C(N2)C3=CC=NC=C3)C4=CC=C(C=C4)F | ||||
| InChI | 1S/C21H16FN3OS/c1-27(26)18-8-4-16(5-9-18)21-24-19(14-2-6-17(22)7-3-14)20(25-21)15-10-12-23-13-11-15/h2-13H,1H3,(H,24,25)/t27-/m0/s1 | ||||
| InChIKey | CDMGBJANTYXAIV-MHZLTWQESA-N | ||||
| PubChem Compound ID | 9543416 | ||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| PDB ID: 3MPA Conformational plasticity of p38 MAP kinase DFG motif mutants in response to inhibitor binding | ||||||
| Method | X-ray diffraction | Resolution | 2.10 Å | Mutation | Yes | [1] |
| PDB Sequence |
RPTFYRQELN
14 KTIWEVPERY24 QNLSPVGSGS37 VCAAFDTKTG47 LRVAVKKLSR57 PFQSIIHAKR 67 TYRELRLLKH77 MKHENVIGLL87 DVFTPARSLE97 EFNDVYLVTH107 LMGADLNNIV 117 KCQKLTDDHV127 QFLIYQILRG137 LKYIHSADII147 HRDLKPSNLA157 VNEDCELKIL 167 GFGTRWYRAP191 EIMLNWMHYN201 QTVDIWSVGC211 IMAELLTGRT221 LFPGTDHIDQ 231 LKLILRLVGT241 PGAELLKKIS251 SESARNYIQS261 LTQMPKMNFA271 NVFIGANPLA 281 VDLLEKMLVL291 DSDKRITAAQ301 ALAHAYFAQY311 HDPDDEPVAD321 PYDQSFESRD 331 LLIDEWKSLT341 YDEVISFVPP351 P
|
|||||
|
|
||||||
| PDB ID: 3GCP Human P38 MAP Kinase in Complex with SB203580 | ||||||
| Method | X-ray diffraction | Resolution | 2.25 Å | Mutation | Yes | [2] |
| PDB Sequence |
ERPTFYRQEL
13 NKTIWEVPER23 YQNLSPVGSG33 AYGSVCAAFD43 TKTGLRVAVK53 KLSRPFQSII 63 HAKRTYRELR73 LLKHMKHENV83 IGLLDVFTPA93 RSLEEFNDVY103 LVTHLMGADL 113 NNIVKSQKLT123 DDHVQFLIYQ133 ILRGLKYIHS143 ADIIHRDLKP153 SNLAVNEDSE 163 LKILDFGLCT185 RWYRAPEIML195 NWMHYNQTVD205 IWSVGCIMAE215 LLTGRTLFPG 225 TDHIDQLKLI235 LRLVGTPGAE245 LLKKISSESA255 RNYIQSLTQM265 PKMNFANVFI 275 GANPLAVDLL285 EKMLVLDSDK295 RITAAQALAH305 AYFAQYHDPD315 DEPVADPYDQ 325 SLESRDLLID335 EWKSLTYDEV345 ISFVPPP
|
|||||
|
|
||||||
| PDB ID: 3OBG Conformational plasticity of p38 MAP kinase DFG mutants in response to inhibitor binding | ||||||
| Method | X-ray diffraction | Resolution | 2.80 Å | Mutation | Yes | [3] |
| PDB Sequence |
RPTFYRQELN
14 KTIWEVPERY24 QNLSPVGGSV38 CAAFDTKTGL48 RVAVKKLSRP58 FQSIIHAKRT 68 YRELRLLKHM78 KHENVIGLLD88 VFTPARSLEE98 FNDVYLVTHL108 MGADLNNIVK 118 CQKLTDDHVQ128 FLIYQILRGL138 KYIHSADIIH148 RDLKPSNLAV158 NEDCELKILD 168 GGLATRWYRA190 PEIMLNWMHY200 NQTVDIWSVG210 CIMAELLTGR220 TLFPGTDHID 230 QLKLILRLVG240 TPGAELLKKI250 SSESARNYIQ260 SLTQMPKMNF270 ANVFIGANPL 280 AVDLLEKMLV290 LDSDKRITAA300 QALAHAYFAQ310 YHDPDDEPVA320 DPYDQSFESR 330 DLLIDEWKSL340 TYDEVISFVP350 PP
|
|||||
|
|
VAL30
4.642
VAL38
3.821
ALA51
3.609
VAL52
4.570
LYS53
3.557
GLU71
4.893
LEU75
3.756
ILE84
4.075
GLY85
4.877
LEU86
4.134
LEU104
3.317
|
|||||
| PDB ID: 3ZS5 Structural basis for kinase selectivity of three clinical p38alpha inhibitors | ||||||
| Method | X-ray diffraction | Resolution | 1.60 Å | Mutation | No | [4] |
| PDB Sequence |
HSQERPTFYR
10 QELNKTIWEV20 PERYQNLSPV30 GSGAYGSVCA40 AFDTKTGLRV50 AVKKLSRPFQ 60 SIIHAKRTYR70 ELRLLKHMKH80 ENVIGLLDVF90 TPARSLEEFN100 DVYLVTHLMG 110 ADLNNIVKCQ120 KLTDDHVQFL130 IYQILRGLKY140 IHSADIIHRD150 LKPSNLAVNE 160 DCELKILDFG170 LATRWYRAPE192 IMLNWMHYNQ202 TVDIWSVGCI212 MAELLTGRTL 222 FPGTDHIDQL232 KLILRLVGTP242 GAELLKKISS252 ESARNYIQSL262 TQMPKMNFAN 272 VFIGANPLAV282 DLLEKMLVLD292 SDKRITAAQA302 LAHAYFAQYH312 DPDDEPVADP 322 YDQSFESRDL332 LIDEWKSLTY342 DEVISFVPPP352
|
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .SB2 or .SB22 or .SB23 or :3SB2;style chemicals stick;color identity;select .A:30 or .A:35 or .A:38 or .A:51 or .A:52 or .A:53 or .A:75 or .A:84 or .A:86 or .A:104 or .A:105 or .A:106 or .A:107 or .A:108 or .A:109 or .A:169 or .A:170 or .A:171; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
||||||
| PDB ID: 1A9U THE COMPLEX STRUCTURE OF THE MAP KINASE P38/SB203580 | ||||||
| Method | X-ray diffraction | Resolution | 2.50 Å | Mutation | No | [5] |
| PDB Sequence |
ERPTFYRQEL
13 NKTIWEVPER23 YQNLSPVGSG33 AYGSVCAAFD43 TKTGLRVAVK53 KLSRPFQSII 63 HAKRTYRELR73 LLKHMKHENV83 IGLLDVFTPA93 RSLEEFNDVY103 LVTHLMGADL 113 NNIVKCQKLT123 DDHVQFLIYQ133 ILRGLKYIHS143 ADIIHRDLKP153 SNLAVNEDCE 163 LKILDFGLAR173 HTDDEMTGYV183 ATRWYRAPEI193 MLNWMHYNQT203 VDIWSVGCIM 213 AELLTGRTLF223 PGTDHIDQLK233 LILRLVGTPG243 AELLKKISSE253 SARNYIQSLT 263 QMPKMNFANV273 FIGANPLAVD283 LLEKMLVLDS293 DKRITAAQAL303 AHAYFAQYHD 313 PDDEPVADPY323 DQSFESRDLL333 IDEWKSLTYD343 EVISFVPPPL353 D |
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .SB2 or .SB22 or .SB23 or :3SB2;style chemicals stick;color identity;select .A:35 or .A:38 or .A:51 or .A:52 or .A:53 or .A:71 or .A:75 or .A:84 or .A:85 or .A:86 or .A:104 or .A:105 or .A:106 or .A:107 or .A:108 or .A:109 or .A:168 or .A:173; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
||||||
| References | Top | ||||
|---|---|---|---|---|---|
| REF 1 | Conformational plasticity of p38 MAP kinase DFG motif mutants in response to inhibitor binding | ||||
| REF 2 | Development of a fluorescent-tagged kinase assay system for the detection and characterization of allosteric kinase inhibitors. J Am Chem Soc. 2009 Sep 23;131(37):13286-96. | ||||
| REF 3 | Conformational plasticity of p38 MAP kinase DFG motif mutants in response to inhibitor binding | ||||
| REF 4 | X-ray structure of p38Alpha bound to TAK-715: comparison with three classic inhibitors. Acta Crystallogr D Biol Crystallogr. 2012 Aug;68(Pt 8):1041-50. | ||||
| REF 5 | Structural basis of inhibitor selectivity in MAP kinases. Structure. 1998 Sep 15;6(9):1117-28. | ||||
If You Find Any Error in Data or Bug in Web Service, Please Kindly Report It to Dr. Zhou and Dr. Zhang.