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 T99057 Target Info
Target Name HUMAN ERK activator kinase 1 (MEK1)
Synonyms PRKMK1; Mitogen-activated protein kinase kinase 1; MKK1; MEK 1; MAPKK 1; MAPK/ERKkinase 1; MAPK/ERK kinase 1; MAP kinase kinase 1; Dual specificity mitogen-activated protein kinase kinase 1
Gene Name MAP2K1
Biochemical Class Kinase
UniProt ID
MP2K1_HUMAN
Ligand General Information  Top
Ligand Name Adenosine triphosphate Ligand Info
Canonical SMILES C1=NC(=C2C(=N1)N(C=N2)C3C(C(C(O3)COP(=O)(O)OP(=O)(O)OP(=O)(O)O)O)O)N
InChI 1S/C10H16N5O13P3/c11-8-5-9(13-2-12-8)15(3-14-5)10-7(17)6(16)4(26-10)1-25-30(21,22)28-31(23,24)27-29(18,19)20/h2-4,6-7,10,16-17H,1H2,(H,21,22)(H,23,24)(H2,11,12,13)(H2,18,19,20)/t4-,6-,7-,10-/m1/s1
InChIKey ZKHQWZAMYRWXGA-KQYNXXCUSA-N
PubChem Compound ID 5957
Drug Binding Sites of Target  Top
PDB ID: 3VVH      X-ray structure of the human mitogen-activated protein kinase kinase 1 (MEK1) in complex with an inhibitor and MgATP
Method X-ray diffraction Resolution 2.00 Å Mutation No [1]
PDB Sequence
MELKDDDFEK
70
ISELGAGNGG
80
VVFKVSHKPS
90
GLVMARKLIH
100
LEIKPAIRNQ
110

IIRELQVLHE
120
CNSPYIVGFY
130
GAFYSDGEIS
140
ICMEHMDGGS
150
LDQVLKKAGR
160

IPEQILGKVS
170
IAVIKGLTYL
180
REKHKIMHRD
190
VKPSNILVNS
200
RGEIKLCDFG
210

VSGQLIDSMA
220
TRSYMSPERL
235
QGTHYSVQSD
245
IWSMGLSLVE
255
MAVGRYPIPP
265

PDAKELELMF
275
PPMAIFELLD
315
YIVNEPPPKL
325
PSGVFSLEFQ
335
DFVNKCLIKN
345

PAERADLKQL
355
MVHAFIKRSD
365
AEEVDFAGWL
375
CSTIGLN
Residue
Distance (Å)
LEU74
3.829
GLY75
3.665
ALA76
3.605
GLY77
3.208
ASN78
2.732
GLY79
4.522
GLY80
3.890
VAL81
4.739
VAL82
3.551
ALA95
3.433
LYS97
2.766
VAL127
4.280
MET143
3.330
Residue
Distance (Å)
GLU144
2.766
HIS145
3.922
MET146
3.003
GLY149
4.395
SER150
3.349
GLN153
2.644
ASP190
4.288
LYS192
2.910
SER194
2.851
ASN195
3.061
LEU197
3.499
CYS207
4.916
ASP208
2.776
PDB ID: 1S9J      X-ray structure of the human mitogen-activated protein kinase kinase 1 (MEK1) in a complex with ligand and MgATP
Method X-ray diffraction Resolution 2.40 Å Mutation No [2]
PDB Sequence
MELKDDDFEK
70
ISELGAGNGG
80
VVFKVSHKPS
90
GLVMARKLIH
100
LEIKPAIRNQ
110

IIRELQVLHE
120
CNSPYIVGFY
130
GAFYSDGEIS
140
ICMEHMDGGS
150
LDQVLKKAGR
160

IPEQILGKVS
170
IAVIKGLTYL
180
REKHKIMHRD
190
VKPSNILVNS
200
RGEIKLCDFG
210

VSGQLIDSMA
220
VGTRSYMSPE
233
RLQGTHYSVQ
243
SDIWSMGLSL
253
VEMAVGRYPI
263

PPPDAKELEL
273
MFPPMAIFEL
313
LDYIVNEPPP
323
KLPSGVFSLE
333
FQDFVNKCLI
343

KNPAERADLK
353
QLMVHAFIKR
363
SDAEEVDFAG
373
WLCSTIGLN
Residue
Distance (Å)
LEU74
4.072
GLY75
3.811
ALA76
3.623
GLY77
2.684
ASN78
3.115
GLY80
3.678
VAL82
3.582
ALA95
3.444
LYS97
2.600
VAL127
4.427
MET143
3.383
GLU144
2.968
Residue
Distance (Å)
HIS145
4.105
MET146
3.224
GLY149
4.589
SER150
2.834
ASP152
3.832
GLN153
3.096
ASP190
4.059
LYS192
2.848
SER194
2.909
ASN195
2.885
LEU197
3.473
ASP208
2.832
PDB ID: 3E8N      X-ray structure of the human mitogen-activated protein kinase kinase 1 (MEK1) complexed with a potent inhibitor RDEA119 and MgATP
Method X-ray diffraction Resolution 2.50 Å Mutation No [3]
PDB Sequence
MELKDDDFEK
70
ISELGAGNGG
80
VVFKVSHKPS
90
GLVMARKLIH
100
LEIKPAIRNQ
110

IIRELQVLHE
120
CNSPYIVGFY
130
GAFYSDGEIS
140
ICMEHMDGGS
150
LDQVLKKAGR
160

IPEQILGKVS
170
IAVIKGLTYL
180
REKHKIMHRD
190
VKPSNILVNS
200
RGEIKLCDFG
210

VSGQLIDSMA
220
NSVGTRSYMS
231
PERLQGTHYS
241
VQSDIWSMGL
251
SLVEMAVGRY
261

PIPPPDAKEL
271
ELMFPPMAIF
311
ELLDYIVNEP
321
PPKLPSGVFS
331
LEFQDFVNKC
341

LIKNPAERAD
351
LKQLMVHAFI
361
KRSDAEEVDF
371
AGWLCSTIGL
381
N
Residue
Distance (Å)
LEU74
3.770
GLY75
4.016
ALA76
3.910
GLY77
3.665
ASN78
3.403
GLY79
4.109
GLY80
3.452
VAL81
4.800
VAL82
3.075
ALA95
3.448
LYS97
2.894
VAL127
4.388
MET143
3.217
GLU144
2.880
Residue
Distance (Å)
HIS145
3.724
MET146
3.096
GLY149
4.549
SER150
2.981
ASP152
3.782
GLN153
2.459
ASP190
4.146
LYS192
3.012
SER194
2.822
ASN195
2.901
LEU197
3.608
CYS207
4.908
ASP208
2.677
PDB ID: 3DY7      X-ray structure of the human mitogen-activated protein kinase kinase 1 (MEK1) in a complex with ligand and MgATP
Method X-ray diffraction Resolution 2.70 Å Mutation No [4]
PDB Sequence
ELKDDDFEKI
71
SELGAGNGGV
81
VFKVSHKPSG
91
LVMARKLIHL
101
EIKPAIRNQI
111

IRELQVLHEC
121
NSPYIVGFYG
131
AFYSDGEISI
141
CMEHMDGGSL
151
DQVLKKAGRI
161

PEQILGKVSI
171
AVIKGLTYLR
181
EKHKIMHRDV
191
KPSNILVNSR
201
GEIKLCDFGV
211

SGQLIDSMAN
221
GTRSYMSPER
234
LQGTHYSVQS
244
DIWSMGLSLV
254
EMAVGRYPIP
264

PPPMAIFELL
314
DYIVNEPPPK
324
LPSGVFSLEF
334
QDFVNKCLIK
344
NPAERADLKQ
354

LMVHAFIKRS
364
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .ATP or .ATP2 or .ATP3 or :3ATP;style chemicals stick;color identity;select .A:74 or .A:75 or .A:76 or .A:77 or .A:78 or .A:80 or .A:81 or .A:82 or .A:95 or .A:97 or .A:127 or .A:143 or .A:144 or .A:145 or .A:146 or .A:149 or .A:150 or .A:152 or .A:153 or .A:190 or .A:192 or .A:194 or .A:195 or .A:197 or .A:207 or .A:208; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
LEU74
3.663
GLY75
3.649
ALA76
4.067
GLY77
3.419
ASN78
3.392
GLY80
3.593
VAL81
4.632
VAL82
4.136
ALA95
3.553
LYS97
2.679
VAL127
4.271
MET143
3.298
GLU144
2.841
Residue
Distance (Å)
HIS145
3.915
MET146
3.145
GLY149
4.612
SER150
2.790
ASP152
4.215
GLN153
2.569
ASP190
4.480
LYS192
2.603
SER194
3.184
ASN195
2.950
LEU197
3.294
CYS207
4.951
ASP208
2.744
PDB ID: 3V04      Discovery of Novel Allosteric MEK Inhibitors Possessing Classical and Non-classical Bidentate Ser212 Interactions.
Method X-ray diffraction Resolution 2.70 Å Mutation No [5]
PDB Sequence
MELKDDDFEK
70
ISELGAGNGG
80
VVFKVSHKPS
90
GLVMARKLIH
100
LEIKPAIRNQ
110

IIRELQVLHE
120
CNSPYIVGFY
130
GAFYSDGEIS
140
ICMEHMDGGS
150
LDQVLKKAGR
160

IPEQILGKVS
170
IAVIKGLTYL
180
REKHKIMHRD
190
VKPSNILVNS
200
RGEIKLCDFG
210

VSGQLIDSMA
220
VGTRSYMSPE
233
RLQGTHYSVQ
243
SDIWSMGLSL
253
VEMAVGRYPI
263

PPPDAKELEL
273
MFPPMAIFEL
313
LDYIVNEPPP
323
KLPSGVFSLE
333
FQDFVNKCLI
343

KNPAERADLK
353
QLMVHAFIKR
363
SDAEEVDFAG
373
WLCSTIGLN
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .ATP or .ATP2 or .ATP3 or :3ATP;style chemicals stick;color identity;select .A:74 or .A:75 or .A:76 or .A:77 or .A:78 or .A:80 or .A:81 or .A:82 or .A:95 or .A:97 or .A:127 or .A:143 or .A:144 or .A:145 or .A:146 or .A:149 or .A:150 or .A:152 or .A:153 or .A:190 or .A:192 or .A:194 or .A:195 or .A:197 or .A:208; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
LEU74
3.856
GLY75
4.033
ALA76
3.577
GLY77
2.550
ASN78
3.571
GLY80
3.465
VAL81
4.956
VAL82
3.528
ALA95
3.430
LYS97
2.533
VAL127
4.550
MET143
3.568
GLU144
3.040
Residue
Distance (Å)
HIS145
3.979
MET146
3.119
GLY149
4.596
SER150
3.149
ASP152
3.690
GLN153
2.733
ASP190
4.241
LYS192
2.558
SER194
2.657
ASN195
3.039
LEU197
3.534
ASP208
2.899
PDB ID: 3V01      Discovery of Novel Allosteric MEK Inhibitors Possessing Classical and Non-classical Bidentate Ser212 Interactions.
Method X-ray diffraction Resolution 2.71 Å Mutation No [5]
PDB Sequence
MELKDDDFEK
70
ISELGAGNGG
80
VVFKVSHKPS
90
GLVMARKLIH
100
LEIKPAIRNQ
110

IIRELQVLHE
120
CNSPYIVGFY
130
GAFYSDGEIS
140
ICMEHMDGGS
150
LDQVLKKAGR
160

IPEQILGKVS
170
IAVIKGLTYL
180
REKHKIMHRD
190
VKPSNILVNS
200
RGEIKLCDFG
210

VSGQLIDSMA
220
VGTRSYMSPE
233
RLQGTHYSVQ
243
SDIWSMGLSL
253
VEMAVGRYPI
263

PPPDAKELEL
273
MFPPMAIFEL
313
LDYIVNEPPP
323
KLPSGVFSLE
333
FQDFVNKCLI
343

KNPAERADLK
353
QLMVHAFIKR
363
SDAEEVDFAG
373
WLCSTIGLN
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .ATP or .ATP2 or .ATP3 or :3ATP;style chemicals stick;color identity;select .A:74 or .A:75 or .A:76 or .A:77 or .A:78 or .A:80 or .A:82 or .A:95 or .A:97 or .A:127 or .A:143 or .A:144 or .A:145 or .A:146 or .A:149 or .A:150 or .A:152 or .A:153 or .A:190 or .A:192 or .A:194 or .A:195 or .A:197 or .A:207 or .A:208; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
LEU74
3.962
GLY75
4.051
ALA76
3.358
GLY77
2.898
ASN78
3.269
GLY80
3.350
VAL82
3.394
ALA95
3.452
LYS97
2.581
VAL127
4.507
MET143
3.596
GLU144
2.897
HIS145
3.924
Residue
Distance (Å)
MET146
3.022
GLY149
4.570
SER150
3.438
ASP152
3.704
GLN153
2.801
ASP190
4.363
LYS192
2.285
SER194
2.810
ASN195
2.820
LEU197
3.775
CYS207
4.992
ASP208
2.761
PDB ID: 3EQB      X-ray structure of the human mitogen-activated protein kinase kinase 1 (MEK1) in a complex with ligand and MgATP
Method X-ray diffraction Resolution 2.62 Å Mutation No [6]
PDB Sequence
MELKDDDFEK
70
ISELGAGNGG
80
VVFKVSHKPS
90
GLVMARKLIH
100
LEIKPAIRNQ
110

IIRELQVLHE
120
CNSPYIVGFY
130
GAFYSDGEIS
140
ICMEHMDGGS
150
LDQVLKKAGR
160

IPEQILGKVS
170
IAVIKGLTYL
180
REKHKIMHRD
190
VKPSNILVNS
200
RGEIKLCDFG
210

VSGQLIDSMA
220
VGTRSYMSPE
233
RLQGTHYSVQ
243
SDIWSMGLSL
253
VEMAVGRYPI
263

PPPDAKELEL
273
MFPPMAIFEL
313
LDYIVNEPPP
323
KLPSGVFSLE
333
FQDFVNKCLI
343

KNPAERADLK
353
QLMVHAFIKR
363
SDAEEVDFAG
373
WLCSTIGLN
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .ATP or .ATP2 or .ATP3 or :3ATP;style chemicals stick;color identity;select .A:74 or .A:75 or .A:76 or .A:77 or .A:78 or .A:80 or .A:81 or .A:82 or .A:95 or .A:97 or .A:127 or .A:143 or .A:144 or .A:145 or .A:146 or .A:149 or .A:150 or .A:152 or .A:153 or .A:190 or .A:192 or .A:194 or .A:195 or .A:197 or .A:207 or .A:208; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
LEU74
3.690
GLY75
3.845
ALA76
3.777
GLY77
2.581
ASN78
4.347
GLY80
3.825
VAL81
3.932
VAL82
3.703
ALA95
3.466
LYS97
2.433
VAL127
4.292
MET143
3.276
GLU144
2.862
Residue
Distance (Å)
HIS145
3.925
MET146
3.040
GLY149
4.584
SER150
2.892
ASP152
4.129
GLN153
2.674
ASP190
3.986
LYS192
2.479
SER194
3.008
ASN195
2.934
LEU197
3.638
CYS207
4.937
ASP208
2.703
PDB ID: 2P55      X-ray structure of the human mitogen-activated protein kinase kinase 1 (MEK1) in a complex with ligand and MgATP
Method X-ray diffraction Resolution 2.80 Å Mutation No [7]
PDB Sequence
MELKDDDFEK
70
ISELGAGNGG
80
VVFKVSHKPS
90
GLVMARKLIH
100
LEIKPAIRNQ
110

IIRELQVLHE
120
CNSPYIVGFY
130
GAFYSDGEIS
140
ICMEHMDGGS
150
LDQVLKKAGR
160

IPEQILGKVS
170
IAVIKGLTYL
180
REKHKIMHRD
190
VKPSNILVNS
200
RGEIKLCDFG
210

VSGQLIDSMA
220
VGTRSYMSPE
233
RLQGTHYSVQ
243
SDIWSMGLSL
253
VEMAVGRYPI
263

PPPDAKELEL
273
MFPPMAIFEL
313
LDYIVNEPPP
323
KLPSGVFSLE
333
FQDFVNKCLI
343

KNPAERADLK
353
QLMVHAFIKR
363
SDAEEVDFAG
373
WLCSTIGLN
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .ATP or .ATP2 or .ATP3 or :3ATP;style chemicals stick;color identity;select .A:74 or .A:75 or .A:76 or .A:77 or .A:78 or .A:80 or .A:81 or .A:82 or .A:95 or .A:97 or .A:127 or .A:143 or .A:144 or .A:145 or .A:146 or .A:147 or .A:149 or .A:150 or .A:152 or .A:153 or .A:190 or .A:192 or .A:194 or .A:195 or .A:197 or .A:208; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
LEU74
3.094
GLY75
3.008
ALA76
3.040
GLY77
2.989
ASN78
3.679
GLY80
3.431
VAL81
4.719
VAL82
2.891
ALA95
3.475
LYS97
2.508
VAL127
3.957
MET143
2.855
GLU144
1.909
Residue
Distance (Å)
HIS145
3.835
MET146
2.088
ASP147
4.159
GLY149
4.091
SER150
1.983
ASP152
3.843
GLN153
2.435
ASP190
4.002
LYS192
2.602
SER194
2.758
ASN195
3.245
LEU197
3.567
ASP208
3.147
PDB ID: 3PP1      Crystal Structure of the Human Mitogen-activated protein kinase kinase 1 (MEK 1) in complex with ligand and MgATP
Method X-ray diffraction Resolution 2.70 Å Mutation No [8]
PDB Sequence
MELKDDDFEK
70
ISELGAGNGG
80
VVFKVSHKPS
90
GLVMARKLIH
100
LEIKPAIRNQ
110

IIRELQVLHE
120
CNSPYIVGFY
130
GAFYSDGEIS
140
ICMEHMDGGS
150
LDQVLKKAGR
160

IPEQILGKVS
170
IAVIKGLTYL
180
REKHKIMHRD
190
VKPSNILVNS
200
RGEIKLCDFG
210

VSGQLIDSMA
220
NSFVGTRSYM
230
SPERLQGTHY
240
SVQSDIWSMG
250
LSLVEMAVGR
260

YPIPPPDAKE
270
LELMFPMAIF
311
ELLDYIVNEP
321
PPKLPSGVFS
331
LEFQDFVNKC
341

LIKNPAERAD
351
LKQLMVHAFI
361
KRSDAEEVDF
371
AGWLCSTIGL
381
N
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .ATP or .ATP2 or .ATP3 or :3ATP;style chemicals stick;color identity;select .A:74 or .A:75 or .A:76 or .A:77 or .A:78 or .A:80 or .A:81 or .A:82 or .A:95 or .A:97 or .A:127 or .A:143 or .A:144 or .A:145 or .A:146 or .A:149 or .A:150 or .A:152 or .A:153 or .A:190 or .A:192 or .A:194 or .A:195 or .A:197 or .A:207 or .A:208 or .A:224; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
LEU74
3.818
GLY75
3.737
ALA76
3.722
GLY77
2.807
ASN78
2.719
GLY80
3.387
VAL81
4.722
VAL82
3.841
ALA95
3.536
LYS97
2.667
VAL127
4.226
MET143
3.386
GLU144
2.922
HIS145
3.964
Residue
Distance (Å)
MET146
3.085
GLY149
4.591
SER150
3.179
ASP152
3.943
GLN153
2.871
ASP190
4.052
LYS192
2.947
SER194
2.695
ASN195
3.085
LEU197
3.532
CYS207
4.767
ASP208
2.603
VAL224
4.012
PDB ID: 3DV3      MEK1 with PF-04622664 Bound
Method X-ray diffraction Resolution 2.30 Å Mutation No [4]
PDB Sequence
MELKDDDFEK
70
ISELGAGNGG
80
VVFKVSHKPS
90
GLVMARKLIH
100
LEIKPAIRNQ
110

IIRELQVLHE
120
CNSPYIVGFY
130
GAFYSDGEIS
140
ICMEHMDGGS
150
LDQVLKKAGR
160

IPEQILGKVS
170
IAVIKGLTYL
180
REKHKIMHRD
190
VKPSNILVNS
200
RGEIKLCDFG
210

VSGQLIDSMA
220
NGTRSYMSPE
233
RLQGTHYSVQ
243
SDIWSMGLSL
253
VEMAVGRYPI
263

PPPDAKELEL
273
MFPMAIFELL
314
DYIVNEPPPK
324
LPSGVFSLEF
334
QDFVNKCLIK
344

NPAERADLKQ
354
LMVHAFIKRS
364
DAEEVDFAGW
374
LCSTIGLN
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .ATP or .ATP2 or .ATP3 or :3ATP;style chemicals stick;color identity;select .A:74 or .A:75 or .A:76 or .A:77 or .A:78 or .A:80 or .A:81 or .A:82 or .A:95 or .A:97 or .A:127 or .A:143 or .A:144 or .A:145 or .A:146 or .A:149 or .A:150 or .A:152 or .A:153 or .A:190 or .A:192 or .A:194 or .A:195 or .A:197 or .A:208; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
LEU74
3.889
GLY75
3.912
ALA76
3.676
GLY77
3.309
ASN78
2.821
GLY80
3.648
VAL81
4.840
VAL82
3.515
ALA95
3.378
LYS97
2.785
VAL127
4.248
MET143
3.279
GLU144
2.943
Residue
Distance (Å)
HIS145
3.970
MET146
3.031
GLY149
4.423
SER150
3.297
ASP152
3.973
GLN153
2.875
ASP190
3.995
LYS192
2.376
SER194
3.085
ASN195
3.100
LEU197
3.442
ASP208
2.720
PDB ID: 3OS3      Mitogen-activated protein kinase kinase 1 (MEK1) in complex with CH4858061 and MgATP
Method X-ray diffraction Resolution 2.80 Å Mutation No [9]
PDB Sequence
ELKDDDFEKI
71
SELGAGNGGV
81
VFKVSHKPSG
91
LVMARKLIHL
101
EIKPAIRNQI
111

IRELQVLHEC
121
NSPYIVGFYG
131
AFYSDGEISI
141
CMEHMDGGSL
151
DQVLKKAGRI
161

PEQILGKVSI
171
AVIKGLTYLR
181
EKHKIMHRDV
191
KPSNILVNSR
201
GEIKLCDFGV
211

SGQLIDSMAN
221
SFVGTRSYMS
231
PERLQGTHYS
241
VQSDIWSMGL
251
SLVEMAVGRY
261

PIPMAIFELL
314
DYIVNEPPPK
324
LPVFSLEFQD
336
FVNKCLIKNP
346
AERADLKQLM
356

VHAFIKRSDA
366
EEVDFAGWLC
376
ST
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .ATP or .ATP2 or .ATP3 or :3ATP;style chemicals stick;color identity;select .A:74 or .A:75 or .A:76 or .A:77 or .A:78 or .A:80 or .A:81 or .A:82 or .A:95 or .A:97 or .A:127 or .A:143 or .A:144 or .A:145 or .A:146 or .A:147 or .A:149 or .A:150 or .A:153 or .A:190 or .A:192 or .A:194 or .A:195 or .A:197 or .A:207 or .A:208; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
LEU74
3.499
GLY75
3.438
ALA76
2.998
GLY77
3.480
ASN78
2.962
GLY80
4.014
VAL81
4.095
VAL82
2.966
ALA95
3.490
LYS97
2.942
VAL127
4.198
MET143
3.566
GLU144
2.679
Residue
Distance (Å)
HIS145
3.922
MET146
2.941
ASP147
4.964
GLY149
4.693
SER150
2.735
GLN153
3.215
ASP190
4.289
LYS192
3.266
SER194
2.878
ASN195
3.128
LEU197
3.544
CYS207
4.610
ASP208
2.713
PDB ID: 4AN3      Crystal structures of human MEK1 with carboxamide-based allosteric inhibitor XL518 (GDC-0973), or related analogs.
Method X-ray diffraction Resolution 2.10 Å Mutation Yes [10]
PDB Sequence
MALGELKDDD
67
FEKISELGAG
77
NGGVVFKVSH
87
KPSGLVMARK
97
LIHLEIKPAI
107

RNQIIRELQV
117
LHECNSPYIV
127
GFYGAFYSDG
137
EISICMEHMD
147
GGSLDQVLKK
157

AGRIPEQILG
167
KVSIAVIKGL
177
TYLREKHKIM
187
HRDVKPSNIL
197
VNSRGEIKLC
207

DFGVSGQLID
217
EMANEGTRSY
229
MSPERLQGTH
239
YSVQSDIWSM
249
GLSLVEMAVG
259

RYPRPPMAIF
311
ELLDYIVNEP
321
PPKLPSAVFS
331
LEFQDFVNKC
341
LIKNPAERAD
351

LKQLMVHAFI
361
KRSDAEEVDF
371
AGWLCSTIGL
381
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .ATP or .ATP2 or .ATP3 or :3ATP;style chemicals stick;color identity;select .A:74 or .A:75 or .A:76 or .A:77 or .A:78 or .A:79 or .A:80 or .A:81 or .A:82 or .A:95 or .A:97 or .A:127 or .A:143 or .A:144 or .A:145 or .A:146 or .A:149 or .A:150 or .A:152 or .A:153 or .A:190 or .A:192 or .A:194 or .A:195 or .A:197 or .A:207 or .A:208 or .A:226; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
LEU74
3.124
GLY75
4.081
ALA76
3.970
GLY77
3.522
ASN78
2.839
GLY79
4.379
GLY80
3.505
VAL81
4.982
VAL82
3.687
ALA95
3.388
LYS97
2.642
VAL127
3.986
MET143
3.417
GLU144
2.938
Residue
Distance (Å)
HIS145
3.953
MET146
3.102
GLY149
4.394
SER150
3.198
ASP152
4.603
GLN153
2.639
ASP190
4.011
LYS192
2.591
SER194
2.591
ASN195
3.099
LEU197
3.549
CYS207
4.785
ASP208
2.822
THR226
4.127
References  Top
REF 1 X-ray structure of the human mitogen-activated protein kinase kinase 1 (MEK1) in complex with an inhibitor and MgATP
REF 2 Structures of human MAP kinase kinase 1 (MEK1) and MEK2 describe novel noncompetitive kinase inhibition. Nat Struct Mol Biol. 2004 Dec;11(12):1192-7.
REF 3 RDEA119/BAY 869766: a potent, selective, allosteric inhibitor of MEK1/2 for the treatment of cancer.Cancer Res.2009 Sep 1;69(17):6839-47.
REF 4 Beyond the MEK-pocket: can current MEK kinase inhibitors be utilized to synthesize novel type III NCKIs? Does the MEK-pocket exist in kinases other than MEK?. Bioorg Med Chem Lett. 2009 Jan 1;19(1):226-9.
REF 5 Discovery of novel allosteric mitogen-activated protein kinase kinase (MEK) 1,2 inhibitors possessing bidentate Ser212 interactions. J Med Chem. 2012 May 24;55(10):4594-604.
REF 6 2-Alkylamino- and alkoxy-substituted 2-amino-1,3,4-oxadiazoles-O-Alkyl benzohydroxamate esters replacements retain the desired inhibition and selectivity against MEK (MAP ERK kinase). Bioorg Med Chem Lett. 2008 Dec 1;18(23):6171-4.
REF 7 4-anilino-5-carboxamido-2-pyridone derivatives as noncompetitive inhibitors of mitogen-activated protein kinase kinase. J Med Chem. 2007 Oct 18;50(21):5090-102.
REF 8 Discovery of TAK-733, a potent and selective MEK allosteric site inhibitor for the treatment of cancer. Bioorg Med Chem Lett. 2011 Mar 1;21(5):1315-9.
REF 9 Design and synthesis of novel allosteric MEK inhibitor CH4987655 as an orally available anticancer agent. Bioorg Med Chem Lett. 2011 Mar 15;21(6):1795-801.
REF 10 Novel Carboxamide-Based Allosteric MEK Inhibitors: Discovery and Optimization Efforts toward XL518 (GDC-0973). ACS Med Chem Lett. 2012 Apr 9;3(5):416-21.

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