Target Binding Site Detail

Content Navigation (  All   None )                                      
Target General Information
Ligand General Information
Drug Binding Sites of Target
References
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
MK14_HUMAN
Ligand General Information  Top
Ligand Name TAK-715 Ligand Info
Canonical SMILES CCC1=NC(=C(S1)C2=CC(=NC=C2)NC(=O)C3=CC=CC=C3)C4=CC=CC(=C4)C
InChI 1S/C24H21N3OS/c1-3-21-27-22(18-11-7-8-16(2)14-18)23(29-21)19-12-13-25-20(15-19)26-24(28)17-9-5-4-6-10-17/h4-15H,3H2,1-2H3,(H,25,26,28)
InChIKey HEKAIDKUDLCBRU-UHFFFAOYSA-N
PubChem Compound ID 9952773
Drug Binding Sites of Target  Top
PDB ID: 3ZSG      X-ray structure of p38alpha bound to TAK-715
Method X-ray diffraction Resolution 1.89 Å Mutation No [1]
PDB Sequence
ERPTFYRQEL
13
NKTIWEVPER
23
YQNLSPVGSG
33
AYGSVCAAFD
43
TKTGLRVAVK
53

KLSRPFQSII
63
HAKRTYRELR
73
LLKHMKHENV
83
IGLLDVFTPA
93
RSLEEFNDVY
103

LVTHLMGADL
113
NNIVKCQKLT
123
DDHVQFLIYQ
133
ILRGLKYIHS
143
ADIIHRDLKP
153

SNLAVNEDCE
163
LKILDFGLAT
185
RWYRAPEIML
195
NWMHYNQTVD
205
IWSVGCIMAE
215

LLTGRTLFPG
225
TDHIDQLKLI
235
LRLVGTPGAE
245
LLKKISSESA
255
RNYIQSLTQM
265

PKMNFANVFI
275
GANPLAVDLL
285
EKMLVLDSDK
295
RITAAQALAH
305
AYFAQYHDPD
315

DEPVADPYDQ
325
SFESRDLLID
335
EWKSLTYDEV
345
ISFVPPP
Residue
Distance (Å)
VAL30
3.207
TYR35
3.873
VAL38
3.892
ALA51
3.287
VAL52
4.434
LYS53
3.154
LEU75
3.497
ILE84
3.618
LEU86
4.709
LEU104
3.530
Residue
Distance (Å)
VAL105
4.139
THR106
3.612
HIS107
3.296
LEU108
3.827
MET109
2.717
GLY110
4.277
PHE169
3.371
GLY170
3.746
LEU171
3.277
PDB ID: 6ANL      Structure-based Design, Synthesis, and Biological Evaluation of Imidazo[1,2-b]pyridazine-based p38 MAP Kinase Inhibitors
Method X-ray diffraction Resolution 2.00 Å Mutation Yes [2]
PDB Sequence
ERPTFYRQEL
13
NKTIWEVPER
23
YQNLSPVGSG
33
AYGSVCAAFD
43
TKTGLRVAVK
53

KLSRPFQSII
63
HAKRTYRELR
73
LLKHMKHENV
83
IGLLDVFTPA
93
RSLEEFNDVY
103

LVTHLMGADL
113
NNIVKSQKLT
123
DDHVQFLIYQ
133
ILRGLKYIHS
143
ADIIHRDLKP
153

SNLAVNEDSE
163
LKILDFGLAA
184
TRWYRAPEIM
194
LNWMHYNQTV
204
DIWSVGCIMA
214

ELLTGRTLFP
224
GTDHIDQLKL
234
ILRLVGTPGA
244
ELLKKISSES
254
ARNYIQSLTQ
264

MPKMNFANVF
274
IGANPLAVDL
284
LEKMLVLDSD
294
KRITAAQALA
304
HAYFAQYHDP
314

DDEPVADPYD
324
QSFESRDLLI
334
DEWKSLTYDE
344
VISFVPPP
Residue
Distance (Å)
VAL30
3.761
TYR35
3.677
VAL38
3.917
ALA51
3.383
VAL52
4.314
LYS53
2.800
LEU75
3.666
ILE84
4.667
GLY85
4.611
LEU86
4.204
LEU104
3.474
Residue
Distance (Å)
VAL105
3.977
THR106
3.512
HIS107
3.340
LEU108
3.876
MET109
2.677
GLY110
4.149
PHE169
3.442
GLY170
3.308
LEU171
3.429
ALA172
2.843
References  Top
REF 1 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 2 Structure-based design, synthesis, and biological evaluation of imidazo[1,2-b]pyridazine-based p38 MAP kinase inhibitors. Bioorg Med Chem. 2018 Feb 1;26(3):647-660.

If You Find Any Error in Data or Bug in Web Service, Please Kindly Report It to Dr. Zhou and Dr. Zhang.