Target Binding Site Detail
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 |
Ligand General Information | Top | ||||
---|---|---|---|---|---|
Ligand Name | AMP-PNP | Ligand Info | |||
Canonical SMILES | C1=NC(=C2C(=N1)N(C=N2)C3C(C(C(O3)COP(=O)(O)OP(=O)(NP(=O)(O)O)O)O)O)N | ||||
InChI | 1S/C10H17N6O12P3/c11-8-5-9(13-2-12-8)16(3-14-5)10-7(18)6(17)4(27-10)1-26-31(24,25)28-30(22,23)15-29(19,20)21/h2-4,6-7,10,17-18H,1H2,(H,24,25)(H2,11,12,13)(H4,15,19,20,21,22,23)/t4-,6-,7-,10-/m1/s1 | ||||
InChIKey | PVKSNHVPLWYQGJ-KQYNXXCUSA-N | ||||
PubChem Compound ID | 33113 |
Drug Binding Sites of Target | Top | |||||
---|---|---|---|---|---|---|
PDB ID: 7M0X Crystal structure of the BRAF:MEK1 kinases in complex with AMPPNP and PD0325901 | ||||||
Method | X-ray diffraction | Resolution | 2.47 Å | Mutation | Yes | [1] |
PDB Sequence |
LELDEQQRKR
49 LEAFLTQKQK59 VGELKDDDFE69 KISELGAGNG79 GVVFKVSHKP89 SGLVMARKLI 99 HLEIKPAIRN109 QIIRELQVLH119 ECNSPYIVGF129 YGAFYSDGEI139 SICMEHMDGG 149 SLDQVLKKAG159 RIPEQILGKV169 SIAVIKGLTY179 LREKHKIMHR189 DVKPSNILVN 199 SRGEIKLCDF209 GVSGQLIDAM219 ANAFVGTRSY229 MSPERLQGTH239 YSVQSDIWSM 249 GLSLVEMAVG259 RYPIPPPDAK269 ELELMPMAIF311 ELLDYIVNEP321 PPKLPSGVFS 331 LEFQDFVNKC341 LIKNPAERAD351 LKQLMVHAFI361 KRSDAEEVDF371 AGWLCSTIGL 381 NQ
|
|||||
|
GLU102
2.965
LEU74
3.740
GLY75
3.804
ALA76
3.730
GLY77
3.166
ASN78
2.928
GLY79
4.473
GLY80
4.200
VAL81
4.663
VAL82
3.608
ALA95
3.461
LYS97
2.706
VAL127
4.218
MET143
3.535
|
|||||
PDB ID: 6PP9 Crystal structure of BRAF:MEK1 complex | ||||||
Method | X-ray diffraction | Resolution | 2.59 Å | Mutation | Yes | [2] |
PDB Sequence |
EELELDEQQR
47 KRLEAFLTQK57 QKVGELKDDD67 FEKISELGAG77 NGGVVFKVSH87 KPSGLVMARK 97 LIHLEIKPAI107 RNQIIRELQV117 LHECNSPYIV127 GFYGAFYSDG137 EISICMEHMD 147 GGSLDQVLKK157 AGRIPEQILG167 KVSIAVIKGL177 TYLREKHKIM187 HRDVKPSNIL 197 VNSRGEIKLC207 DFGVSGQLID217 AMANAFVGTR227 SYMSPERLQG237 THYSVQSDIW 247 SMGLSLVEMA257 VGRYPIPPPD267 AKELELMPMA309 IFELLDYIVN319 EPPPKLPSGV 329 FSLEFQDFVN339 KCLIKNPAER349 ADLKQLMVHA359 FIKRSDAEEV369 DFAGWLCSTI 379 GLNQ
|
|||||
|
GLU102
2.919
LEU74
3.581
GLY75
3.800
ALA76
3.865
GLY77
3.182
ASN78
2.704
GLY79
4.250
GLY80
4.220
VAL81
4.677
VAL82
3.514
ALA95
3.345
LYS97
2.923
VAL127
4.293
MET143
3.547
|
|||||
PDB ID: 7M0U Crystal structure of the BRAF:MEK1 kinases in complex with AMPPNP and Binimetinib | ||||||
Method | X-ray diffraction | Resolution | 3.09 Å | Mutation | Yes | [1] |
PDB Sequence |
DEQQRKRLEA
52 FLTQKQKVGE62 LKDDDFEKIS72 ELGAGNGGVV82 FKVSHKPSGL92 VMARKLIHLE 102 IKPAIRNQII112 RELQVLHECN122 SPYIVGFYGA132 FYSDGEISIC142 MEHMDGGSLD 152 QVLKKAGRIP162 EQILGKVSIA172 VIKGLTYLRE182 KHKIMHRDVK192 PSNILVNSRG 202 EIKLCDFGVS212 GQLIDAMANA222 FVGTRSYMSP232 ERLQGTHYSV242 QSDIWSMGLS 252 LVEMAVGRYP262 IPPPDAKELE272 LMPMAIFELL314 DYIVNEPPPK324 LPSGVFSLEF 334 QDFVNKCLIK344 NPAERADLKQ354 LMVHAFIKRS364 DAEEVDFAGW374 LCSTIGLNQP 384 S
|
|||||
|
GLU102
3.090
PHE223
4.165
LEU74
3.636
GLY75
3.376
ALA76
3.848
GLY77
3.511
ASN78
3.288
GLY79
4.338
GLY80
4.044
VAL81
4.871
VAL82
3.384
ALA95
3.413
LYS97
2.942
VAL127
4.670
|
|||||
PDB ID: 7M0W Crystal structure of the BRAF:MEK1 kinases in complex with AMPPNP and Pimasertib | ||||||
Method | X-ray diffraction | Resolution | 3.09 Å | Mutation | Yes | [1] |
PDB Sequence |
LDEQQRKRLE
51 AFLTQKQKVG61 ELKDDDFEKI71 SELGAGNGGV81 VFKVSHKPSG91 LVMARKLIHL 101 EIKPAIRNQI111 IRELQVLHEC121 NSPYIVGFYG131 AFYSDGEISI141 CMEHMDGGSL 151 DQVLKKAGRI161 PEQILGKVSI171 AVIKGLTYLR181 EKHKIMHRDV191 KPSNILVNSR 201 GEIKLCDFGV211 SGQLIDAMAN221 AFVGTRSYMS231 PERLQGTHYS241 VQSDIWSMGL 251 SLVEMAVGRY261 PIPPPDAKEL271 ELMPMAIFEL313 LDYIVNEPPP323 KLPSGVFSLE 333 FQDFVNKCLI343 KNPAERADLK353 QLMVHAFIKR363 SDAEEVDFAG373 WLCSTIGLNQ 383
|
|||||
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .ANP or .ANP2 or .ANP3 or :3ANP;style chemicals stick;color identity;select .B:74 or .B:75 or .B:76 or .B:77 or .B:78 or .B:79 or .B:80 or .B:82 or .B:95 or .B:97 or .B:127 or .B:143 or .B:144 or .B:145 or .B:146 or .B:149 or .B:150 or .B:152 or .B:153 or .B:190 or .B:192 or .B:194 or .B:195 or .B:197 or .B:208 or .B:102 or .B:223; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
LEU74
3.643
GLY75
3.557
ALA76
3.358
GLY77
3.387
ASN78
2.750
GLY79
4.126
GLY80
4.525
VAL82
3.519
ALA95
3.346
LYS97
3.381
VAL127
4.592
MET143
3.155
GLU144
3.281
HIS145
4.200
|
|||||
PDB ID: 6V2W Crystal structure of the BRAF:MEK1 kinases in complex with AMPPNP | ||||||
Method | X-ray diffraction | Resolution | 3.12 Å | Mutation | Yes | [1] |
PDB Sequence |
LELDEQQRKR
49 LEAFLTQKQK59 VGELKDDDFE69 KISELGAGNG79 GVVFKVSHKP89 SGLVMARKLI 99 HLEIKPAIRN109 QIIRELQVLH119 ECNSPYIVGF129 YGAFYSDGEI139 SICMEHMDGG 149 SLDQVLKKAG159 RIPEQILGKV169 SIAVIKGLTY179 LREKHKIMHR189 DVKPSNILVN 199 SRGEIKLCDF209 GVSGQLIDAM219 ANAFVGTRSY229 MSPERLQGTH239 YSVQSDIWSM 249 GLSLVEMAVG259 RYPIPPPDAK269 ELELMPMAIF311 ELLDYIVNEP321 PPKLPSGVFS 331 LEFQDFVNKC341 LIKNPAERAD351 LKQLMVHAFI361 KRSDAEEVDF371 AGWLCSTIGL 381 NQ
|
|||||
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .ANP or .ANP2 or .ANP3 or :3ANP;style chemicals stick;color identity;select .B:102 or .B:223 or .B:74 or .B:75 or .B:76 or .B:77 or .B:78 or .B:79 or .B:82 or .B:95 or .B:97 or .B:127 or .B:143 or .B:144 or .B:145 or .B:146 or .B:149 or .B:150 or .B:152 or .B:153 or .B:190 or .B:192 or .B:194 or .B:195 or .B:197 or .B:208; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
GLU102
3.504
PHE223
4.831
LEU74
3.688
GLY75
3.711
ALA76
3.393
GLY77
3.738
ASN78
3.719
GLY79
4.730
VAL82
3.664
ALA95
3.358
LYS97
2.752
VAL127
4.408
MET143
3.310
|
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PDB ID: 7M0Z Crystal structure of the BRAF:MEK1 kinases in complex with AMPPNP and CH5126766 | ||||||
Method | X-ray diffraction | Resolution | 3.12 Å | Mutation | Yes | [1] |
PDB Sequence |
LDEQQRKRLE
51 AFLTQKQKVG61 ELKDDDFEKI71 SELGAGNGGV81 VFKVSHKPSG91 LVMARKLIHL 101 EIKPAIRNQI111 IRELQVLHEC121 NSPYIVGFYG131 AFYSDGEISI141 CMEHMDGGSL 151 DQVLKKAGRI161 PEQILGKVSI171 AVIKGLTYLR181 EKHKIMHRDV191 KPSNILVNSR 201 GEIKLCDFGV211 SGQLIDAMAN221 AFVGTRSYMS231 PERLQGTHYS241 VQSDIWSMGL 251 SLVEMAVGRY261 PIPPPDAKEL271 ELMPMAIFEL313 LDYIVNEPPP323 KLPSGVFSLE 333 FQDFVNKCLI343 KNPAERADLK353 QLMVHAFIKR363 SDAEEVDFAG373 WLCSTIGLNQ 383
|
|||||
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .ANP or .ANP2 or .ANP3 or :3ANP;style chemicals stick;color identity;select .B:102 or .B:223 or .B:74 or .B:75 or .B:76 or .B:77 or .B:78 or .B:79 or .B:80 or .B:81 or .B:82 or .B:95 or .B:97 or .B:143 or .B:144 or .B:145 or .B:146 or .B:149 or .B:150 or .B:152 or .B:153 or .B:190 or .B:192 or .B:194 or .B:195 or .B:197 or .B:208; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
GLU102
3.315
PHE223
4.299
LEU74
3.824
GLY75
2.999
ALA76
3.310
GLY77
2.822
ASN78
2.612
GLY79
2.512
GLY80
3.332
VAL81
4.357
VAL82
3.650
ALA95
3.453
LYS97
2.769
MET143
4.180
|
|||||
PDB ID: 7M0V Crystal structure of the BRAF:MEK1 kinases in complex with AMPPNP and Cobimetinib | ||||||
Method | X-ray diffraction | Resolution | 3.16 Å | Mutation | Yes | [1] |
PDB Sequence |
LDEQQRKRLE
51 AFLTQKQKVG61 ELKDDDFEKI71 SELGAGNGGV81 VFKVSHKPSG91 LVMARKLIHL 101 EIKPAIRNQI111 IRELQVLHEC121 NSPYIVGFYG131 AFYSDGEISI141 CMEHMDGGSL 151 DQVLKKAGRI161 PEQILGKVSI171 AVIKGLTYLR181 EKHKIMHRDV191 KPSNILVNSR 201 GEIKLCDFGV211 SGQLIDAMAN221 AFVGTRSYMS231 PERLQGTHYS241 VQSDIWSMGL 251 SLVEMAVGRY261 PIPPPDAKEL271 ELMPMAIFEL313 LDYIVNEPPP323 KLPSGVFSLE 333 FQDFVNKCLI343 KNPAERADLK353 QLMVHAFIKR363 SDAEEVDFAG373 WLCSTIGLNQ 383
|
|||||
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .ANP or .ANP2 or .ANP3 or :3ANP;style chemicals stick;color identity;select .B:102 or .B:74 or .B:75 or .B:76 or .B:77 or .B:78 or .B:79 or .B:80 or .B:81 or .B:82 or .B:95 or .B:97 or .B:127 or .B:143 or .B:144 or .B:145 or .B:146 or .B:149 or .B:150 or .B:153 or .B:192 or .B:194 or .B:195 or .B:197 or .B:207 or .B:208 or .B:219; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
GLU102
2.996
LEU74
3.108
GLY75
3.246
ALA76
3.025
GLY77
3.193
ASN78
3.277
GLY79
3.282
GLY80
3.594
VAL81
4.958
VAL82
3.167
ALA95
3.453
LYS97
3.024
VAL127
4.708
MET143
3.318
|
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PDB ID: 7M0T Crystal structure of the BRAF:MEK1 kinases in complex with AMPPNP and Selumetinib | ||||||
Method | X-ray diffraction | Resolution | 3.19 Å | Mutation | Yes | [1] |
PDB Sequence |
LDEQQRKRLE
51 AFLTQKQKVG61 ELKDDDFEKI71 SELGAGNGGV81 VFKVSHKPSG91 LVMARKLIHL 101 EIKPAIRNQI111 IRELQVLHEC121 NSPYIVGFYG131 AFYSDGEISI141 CMEHMDGGSL 151 DQVLKKAGRI161 PEQILGKVSI171 AVIKGLTYLR181 EKHKIMHRDV191 KPSNILVNSR 201 GEIKLCDFGV211 SGQLIDAMAN221 AFVGTRSYMS231 PERLQGTHYS241 VQSDIWSMGL 251 SLVEMAVGRY261 PIPPPDAKEL271 ELMPMAIFEL313 LDYIVNEPPP323 KLPSGVFSLE 333 FQDFVNKCLI343 KNPAERADLK353 QLMVHAFIKR363 SDAEEVDFAG373 WLCSTIGLNQ 383
|
|||||
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .ANP or .ANP2 or .ANP3 or :3ANP;style chemicals stick;color identity;select .B:74 or .B:75 or .B:76 or .B:77 or .B:78 or .B:79 or .B:80 or .B:81 or .B:82 or .B:95 or .B:97 or .B:127 or .B:143 or .B:144 or .B:145 or .B:146 or .B:149 or .B:150 or .B:152 or .B:153 or .B:190 or .B:192 or .B:194 or .B:195 or .B:197 or .B:208 or .B:102 or .B:223; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
LEU74
3.681
GLY75
3.478
ALA76
3.245
GLY77
3.273
ASN78
3.044
GLY79
4.358
GLY80
4.062
VAL81
4.907
VAL82
3.684
ALA95
3.546
LYS97
2.896
VAL127
4.806
MET143
3.118
GLU144
3.332
|
|||||
PDB ID: 7M0Y Crystal structure of the BRAF:MEK1 kinases in complex with AMPPNP and Trametinib | ||||||
Method | X-ray diffraction | Resolution | 3.45 Å | Mutation | Yes | [1] |
PDB Sequence |
DEQQRKRLEA
52 FLTQKQKVGE62 LKDDDFEKIS72 ELGAGNGGVV82 FKVSHKPSGL92 VMARKLIHLE 102 IKPAIRNQII112 RELQVLHECN122 SPYIVGFYGA132 FYSDGEISIC142 MEHMDGGSLD 152 QVLKKAGRIP162 EQILGKVSIA172 VIKGLTYLRE182 KHKIMHRDVK192 PSNILVNSRG 202 EIKLCDFGVS212 GQLIDAMANA222 FVGTRSYMSP232 ERLQGTHYSV242 QSDIWSMGLS 252 LVEMAVGRYP262 IPPPDAKELE272 LMPMAIFELL314 DYIVNEPPPK324 LPSGVFSLEF 334 QDFVNKCLIK344 NPAERADLKQ354 LMVHAFIKRS364 DAEEVDFAGW374 LCSTIGLN |
|||||
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .ANP or .ANP2 or .ANP3 or :3ANP;style chemicals stick;color identity;select .B:102 or .B:223 or .B:74 or .B:75 or .B:76 or .B:77 or .B:78 or .B:79 or .B:80 or .B:82 or .B:95 or .B:97 or .B:127 or .B:143 or .B:144 or .B:145 or .B:146 or .B:149 or .B:150 or .B:152 or .B:153 or .B:190 or .B:192 or .B:194 or .B:195 or .B:197 or .B:207 or .B:208; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
GLU102
3.552
PHE223
4.777
LEU74
3.767
GLY75
3.700
ALA76
3.438
GLY77
3.632
ASN78
3.297
GLY79
4.195
GLY80
4.429
VAL82
3.525
ALA95
3.299
LYS97
2.979
VAL127
4.536
MET143
3.126
|
|||||
PDB ID: 5YT3 Structure of the Human Mitogen-Activated Protein Kinase Kinase 1 S218D and S222D mutant | ||||||
Method | X-ray diffraction | Resolution | 2.90 Å | Mutation | Yes | [3] |
PDB Sequence |
ELELDEQQRK
48 RLEAFLTQKQ58 KVGELKDDDF68 EKISELGAGN78 GGVVFKVSHK88 PSGLVMARKL 98 IHLEIKPAIR108 NQIIRELQVL118 HECNSPYIVG128 FYGAFYSDGE138 ISICMEHMDG 148 GSLDQVLKKA158 GRIPEQILGK168 VSIAVIKGLT178 YLREKHKIMH188 RDVKPSNILV 198 NSRGEIKLCD208 FGVTRSYMSP232 ERLQYSVQSD245 IWSMGLSLVE255 MAVGRYPIPP 265 PDAKELELMF275 GPMAIFELLD315 YIVNEPPPKL325 PSGVFSLEFQ335 DFVNKCLIKN 345 PAERADLKQL355 MVHAFIKRSD365 AEEVDFAGWL375 CSTIGLN
|
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Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .ANP or .ANP2 or .ANP3 or :3ANP;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: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
|
LEU74
3.732
GLY75
3.902
ALA76
3.588
GLY77
3.857
ASN78
4.223
GLY80
3.073
VAL82
3.586
ALA95
3.340
LYS97
3.019
VAL127
4.229
MET143
3.221
GLU144
3.158
|
|||||
PDB ID: 4U81 MEK1 Kinase bound to small molecule inhibitor G659 | ||||||
Method | X-ray diffraction | Resolution | 2.70 Å | Mutation | No | [4] |
PDB Sequence |
MELKDDDFEK
70 ISELGAGNGG80 VVFKVSHKPS90 GLVMARKLIH100 LEIKPAIRNQ110 IIRELQVLHE 120 CNSPYIVGFY130 GAFYSDGEIS140 ICMEHMDGGS150 LDQVLKKAGR160 IPEQILGKVS 170 IAVIKGLTYL180 REKHKIMHRD190 VKPSNILVNS200 RGEIKLCDFG210 VSGQLIDSMA 220 VGTRSYMSPE233 RLQGTHYSVQ243 SDIWSMGLSL253 VEMAVGRYPI263 PPPDAKELEL 273 MFPPMAIFEL313 LDYIVNEPPP323 KLPSGVFSLE333 FQDFVNKCLI343 KNPAERADLK 353 QLMVHAFIKR363 SDAEEVDFAG373 WLCSTIGLN
|
|||||
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .ANP or .ANP2 or .ANP3 or :3ANP;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
|
LEU74
3.196
GLY75
3.327
ALA76
3.525
GLY77
2.910
ASN78
3.676
GLY80
3.617
VAL81
4.446
VAL82
3.664
ALA95
3.397
LYS97
2.528
VAL127
4.437
MET143
3.373
GLU144
3.027
|
|||||
PDB ID: 4LMN Crystal Structure of MEK1 kinase bound to GDC0973 | ||||||
Method | X-ray diffraction | Resolution | 2.80 Å | Mutation | No | [5] |
PDB Sequence |
MELKDDDFEK
70 ISELGAGNGG80 VVFKVSHKPS90 GLVMARKLIH100 LEIKPAIRNQ110 IIRELQVLHE 120 CNSPYIVGFY130 GAFYSDGEIS140 ICMEHMDGGS150 LDQVLKKAGR160 IPEQILGKVS 170 IAVIKGLTYL180 REKHKIMHRD190 VKPSNILVNS200 RGEIKLCDFG210 VSGQLIDSMA 220 NSFVGTRSYM230 SPERLQGTHY240 SVQSDIWSMG250 LSLVEMAVGR260 YPIPPPDAKE 270 LELMFPPMAI310 FELLDYIVNE320 PPPKLPSGVF330 SLEFQDFVNK340 CLIKNPAERA 350 DLKQLMVHAF360 IKRSDAEEVD370 FAGWLCSTIG380 LN
|
|||||
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .ANP or .ANP2 or .ANP3 or :3ANP;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
|
LEU74
3.254
GLY75
3.461
ALA76
3.509
GLY77
2.759
ASN78
3.738
GLY80
3.236
VAL82
3.131
ALA95
3.489
LYS97
2.795
VAL127
4.148
MET143
3.298
GLU144
2.796
HIS145
3.848
|
|||||
PDB ID: 4U80 MEK 1 kinase bound to G799 | ||||||
Method | X-ray diffraction | Resolution | 2.80 Å | Mutation | No | [4] |
PDB Sequence |
MELKDDDFEK
70 ISELGAGNGG80 VVFKVSHKPS90 GLVMARKLIH100 LEIKPAIRNQ110 IIRELQVLHE 120 CNSPYIVGFY130 GAFYSDGEIS140 ICMEHMDGGS150 LDQVLKKAGR160 IPEQILGKVS 170 IAVIKGLTYL180 REKHKIMHRD190 VKPSNILVNS200 RGEIKLCDFG210 VSGQLIDSMA 220 VGTRSYMSPE233 RLQGTHYSVQ243 SDIWSMGLSL253 VEMAVGRYPI263 PPPDAKELEL 273 MFPPMAIFEL313 LDYIVNEPPP323 KLPSGVFSLE333 FQDFVNKCLI343 KNPAERADLK 353 QLMVHAFIKR363 SDAEEVDFAG373 WLCSTI
|
|||||
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .ANP or .ANP2 or .ANP3 or :3ANP;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
|
LEU74
3.129
GLY75
3.545
ALA76
3.450
GLY77
3.365
ASN78
3.184
GLY80
3.209
VAL81
4.355
VAL82
3.765
ALA95
3.360
LYS97
2.221
VAL127
4.478
MET143
3.331
GLU144
2.985
|
|||||
PDB ID: 4U7Z Mitogen-Activated Protein Kinase Kinase (MEK1) bound to G805 | ||||||
Method | X-ray diffraction | Resolution | 2.81 Å | Mutation | No | [4] |
PDB Sequence |
MELKDDDFEK
70 ISELGAGNGG80 VVFKVSHKPS90 GLVMARKLIH100 LEIKPAIRNQ110 IIRELQVLHE 120 CNSPYIVGFY130 GAFYSDGEIS140 ICMEHMDGGS150 LDQVLKKAGR160 IPEQILGKVS 170 IAVIKGLTYL180 REKHKIMHRD190 VKPSNILVNS200 RGEIKLCDFG210 VSGQLIDSMA 220 NSVGTRSYMS231 PERLQGTHYS241 VQSDIWSMGL251 SLVEMAVGRY261 PIPPPDAKEL 271 ELMFPPMAIF311 ELLDYIVNEP321 PPKLPSGVFS331 LEFQDFVNKC341 LIKNPAERAD 351 LKQLMVHAFI361 KRSDAEEVDF371 AGWLCSTIGL381 N
|
|||||
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .ANP or .ANP2 or .ANP3 or :3ANP;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
|
LEU74
3.065
GLY75
3.483
ALA76
3.289
GLY77
2.997
ASN78
3.862
GLY80
3.388
VAL81
4.473
VAL82
3.279
ALA95
3.473
LYS97
2.369
VAL127
4.453
MET143
3.276
GLU144
2.940
|
|||||
PDB ID: 7B7R MEK1 in complex with compound 4 | ||||||
Method | X-ray diffraction | Resolution | 1.70 Å | Mutation | No | [6] |
PDB Sequence |
LYFQLEELEL
42 DEQQRKRLEA52 FLTQKQKVGE62 LKDDDFEKIS72 ELGAGNGGVV82 FKVSHKPSGL 92 VMARKLIHLE102 IKPAIRNQII112 RELQVLHECN122 SPYIVGFYGA132 FYSDGEISIC 142 MEHMDGGSLD152 QVLKKAGRIP162 EQILGKVSIA172 VIKGLTYLRE182 KHKIMHRDVK 192 PSNILVNSRG202 EIKLCDFGVS212 GQLIDSMGTR227 SYMSPERLQG237 THYSVQSDIW 247 SMGLSLVEMA257 VGRYPIMAIF311 ELLDYIVNEP321 PPKLPSGVFS331 LEFQDFVNKC 341 LIKNPAERAD351 LKQLMVHAFI361 KRSDAEEVDF371 AGWLCSTIGL381 N |
|||||
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .ANP or .ANP2 or .ANP3 or :3ANP;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; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
LEU74
3.802
GLY75
3.430
ALA76
3.338
GLY77
3.292
ASN78
4.748
GLY79
4.612
GLY80
3.671
VAL81
4.564
VAL82
3.565
ALA95
3.381
LYS97
2.715
VAL127
3.960
MET143
3.593
GLU144
2.898
|
|||||
PDB ID: 7B9L MEK1 in complex with compound 23 | ||||||
Method | X-ray diffraction | Resolution | 1.70 Å | Mutation | No | [6] |
PDB Sequence |
LYFQLEELEL
42 DEQQRKRLEA52 FLTQKQKVGE62 LKDDDFEKIS72 ELGAGNGGVV82 FKVSHKPSGL 92 VMARKLIHLE102 IKPAIRNQII112 RELQVLHECN122 SPYIVGFYGA132 FYSDGEISIC 142 MEHMDGGSLD152 QVLKKAGRIP162 EQILGKVSIA172 VIKGLTYLRE182 KHKIMHRDVK 192 PSNILVNSRG202 EIKLCDFGVS212 GQLIDSMRSY229 MSPERLQGTH239 YSVQSDIWSM 249 GLSLVEMAVG259 RYPIMAIFEL313 LDYIVNEPPP323 KLPSGVFSLE333 FQDFVNKCLI 343 KNPAERADLK353 QLMVHAFIKR363 SDAEEVDFAG373 WLCSTIGLN
|
|||||
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .ANP or .ANP2 or .ANP3 or :3ANP;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; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
LEU74
3.846
GLY75
3.591
ALA76
3.421
GLY77
3.250
ASN78
4.882
GLY79
4.710
GLY80
3.559
VAL81
4.505
VAL82
3.646
ALA95
3.322
LYS97
2.741
VAL127
3.959
MET143
3.629
GLU144
2.888
|
|||||
PDB ID: 7B94 MEK1 in complex with compound 6 | ||||||
Method | X-ray diffraction | Resolution | 2.00 Å | Mutation | No | [6] |
PDB Sequence |
LYFQLEELEL
42 DEQQRKRLEA52 FLTQKQKVGE62 LKDDDFEKIS72 ELGAGNGGVV82 FKVSHKPSGL 92 VMARKLIHLE102 IKPAIRNQII112 RELQVLHECN122 SPYIVGFYGA132 FYSDGEISIC 142 MEHMDGGSLD152 QVLKKAGRIP162 EQILGKVSIA172 VIKGLTYLRE182 KHKIMHRDVK 192 PSNILVNSRG202 EIKLCDFGVS212 GQLIDSMGTR227 SYMSPERLQG237 THYSVQSDIW 247 SMGLSLVEMA257 VGRYPIMAIF311 ELLDYIVNEP321 PPKLPSGVFS331 LEFQDFVNKC 341 LIKNPAERAD351 LKQLMVHAFI361 KRSDAEEVDF371 AGWLCSTIGL381 N |
|||||
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .ANP or .ANP2 or .ANP3 or :3ANP;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; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
LEU74
3.712
GLY75
3.528
ALA76
3.529
GLY77
3.159
ASN78
4.398
GLY79
4.445
GLY80
3.622
VAL81
4.518
VAL82
3.364
ALA95
3.407
LYS97
2.794
VAL127
4.045
MET143
3.340
GLU144
2.824
|
|||||
PDB ID: 7B3M MEK1 in complex with compound 6 | ||||||
Method | X-ray diffraction | Resolution | 2.30 Å | Mutation | No | [6] |
PDB Sequence |
LYFQLEELEL
42 DEQQRKRLEA52 FLTQKQKVGE62 LKDDDFEKIS72 ELGAGNGGVV82 FKVSHKPSGL 92 VMARKLIHLE102 IKPAIRNQII112 RELQVLHECN122 SPYIVGFYGA132 FYSDGEISIC 142 MEHMDGGSLD152 QVLKKAGRIP162 EQILGKVSIA172 VIKGLTYLRE182 KHKIMHRDVK 192 PSNILVNSRG202 EIKLCDFGVS212 GQLIDSMGTR227 SYMSPERLQG237 THYSVQSDIW 247 SMGLSLVEMA257 VGRYPIGMAI310 FELLDYIVNE320 PPPKLPSGVF330 SLEFQDFVNK 340 CLIKNPAERA350 DLKQLMVHAF360 IKRSDAEEVD370 FAGWLCSTIG380 LN |
|||||
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .ANP or .ANP2 or .ANP3 or :3ANP;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; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
LEU74
3.666
GLY75
3.490
ALA76
3.347
GLY77
3.156
ASN78
4.539
GLY79
4.638
GLY80
3.351
VAL81
4.436
VAL82
3.210
ALA95
3.464
LYS97
2.893
VAL127
3.957
MET143
3.406
GLU144
2.808
|
|||||
PDB ID: 3WIG Human MEK1 kinase in complex with CH5126766 and MgAMP-PNP | ||||||
Method | X-ray diffraction | Resolution | 2.70 Å | Mutation | No | [7] |
PDB Sequence |
MELKDDDFEK
71 ISELGAGVVF84 KVSHKPSGLV94 MARKLIHLEI104 KPAIRNQIIR114 ELQVLHECNS 124 PYIVGFYGAF134 YSDGEISICM144 EHMDGGSLDQ154 VLKKAGRIPE164 QILGKVSIAV 174 IKGLTYLREK184 HKIMHRDVKP194 SNILVNSRGE204 IKLCDFGVSG214 QLIDSMANSF 224 VGTRSYMSPE234 RLQGTHYSVQ244 SDIWSMGLSL254 VEMAVGRYPI264 PPPPPMAIFE 312 LLDYIVNEPP322 PKLPSGVFSL332 EFQDFVNKCL342 IKNPAERADL352 KQLMVHAFIK 362 RSDAEEVDFA372 GWLCSTIG
|
|||||
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .ANP or .ANP2 or .ANP3 or :3ANP;style chemicals stick;color identity;select .A:75 or .A:76 or .A:77 or .A:78 or .A:82 or .A:83 or .A:96 or .A:98 or .A:128 or .A:144 or .A:145 or .A:146 or .A:147 or .A:150 or .A:151 or .A:154 or .A:191 or .A:193 or .A:195 or .A:196 or .A:198 or .A:209; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
LEU75
3.660
GLY76
3.711
ALA77
3.617
GLY78
3.302
VAL82
4.583
VAL83
3.744
ALA96
3.252
LYS98
2.730
VAL128
4.502
MET144
4.113
GLU145
2.869
|
|||||
PDB ID: 3ORN Mitogen-activated protein kinase kinase 1 (MEK1) in complex with CH4987655 and MgAMP-PNP | ||||||
Method | X-ray diffraction | Resolution | 2.80 Å | Mutation | No | [8] |
PDB Sequence |
MELKDDDFEK
70 ISELGAGNGG80 VVFKVSHKPS90 GLVMARKLIH100 LEIKPAIRNQ110 IIRELQVLHE 120 CNSPYIVGFY130 GAFYSDGEIS140 ICMEHMDGGS150 LDQVLKKAGR160 IPEQILGKVS 170 IAVIKGLTYL180 REKHKIMHRD190 VKPSNILVNS200 RGEIKLCDFG210 VSGQLIDSMA 220 NSFVGTRSYM230 SPERLQGTHY240 SVQSDIWSMG250 LSLVEMAVGR260 YPIPPPPMAI 310 FELLDYIVNE320 PPPKLPSGVF330 SLEFQDFVNK340 CLIKNPAERA350 DLKQLMVHAF 360 IKRSDAEEVD370 FAGWLCSTIG380
|
|||||
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .ANP or .ANP2 or .ANP3 or :3ANP;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: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
|
LEU74
3.751
GLY75
3.469
ALA76
3.713
GLY77
3.222
ASN78
2.749
GLY79
3.501
GLY80
3.946
VAL81
4.829
VAL82
3.328
ALA95
3.567
LYS97
2.932
VAL127
4.355
MET143
3.604
|
|||||
PDB ID: 3SLS Crystal Structure of human MEK-1 kinase in complex with UCB1353770 and AMPPNP | ||||||
Method | X-ray diffraction | Resolution | 2.30 Å | Mutation | No | [9] |
PDB Sequence |
MTLQQRKRLE
51 AFLTQKQKVG61 ELKDDDFEKI71 SELGAGNGGV81 VFKVSHKPSG91 LVMARKLIHL 101 EIKPAIRNQI111 IRELQVLHEC121 NSPYIVGFYG131 AFYSDGEISI141 CMEHMDGGSL 151 DQVLKKAGRI161 PEQILGKVSI171 AVIKGLTYLR181 EKHKIMHRDV191 KPSNILVNSR 201 GEIKLCDFGV211 SGQLIFVGTR227 SYMSPERLQG237 THYSVQSDIW247 SMGLSLVEMA 257 VGRYPIGAIF273 ELLDYIVNEP283 PPKLPSGVFS293 LEFQDFVNKC303 LIKNPAERAD 313 LKQLMVHAFI323 KRSDAEEVDF333 AGWLCSTIGL343 NQ
|
|||||
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .ANP or .ANP2 or .ANP3 or :3ANP;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
|
LEU74
3.785
GLY75
3.868
ALA76
3.359
GLY77
3.499
ASN78
2.279
GLY80
3.418
VAL81
4.650
VAL82
3.429
ALA95
3.349
LYS97
2.813
VAL127
4.292
MET143
3.557
GLU144
2.766
|
References | Top | ||||
---|---|---|---|---|---|
REF 1 | Allosteric MEK inhibitors act on BRAF/MEK complexes to block MEK activation. Proc Natl Acad Sci U S A. 2021 Sep 7;118(36):e2107207118. | ||||
REF 2 | Architecture of autoinhibited and active BRAF-MEK1-14-3-3 complexes. Nature. 2019 Nov;575(7783):545-550. | ||||
REF 3 | Structure of the Human Mitogen-Activated Protein Kinase Kinase 1 S218D and S222D mutant | ||||
REF 4 | Structure based design of novel 6,5 heterobicyclic mitogen-activated protein kinase kinase (MEK) inhibitors leading to the discovery of imidazo[1,5-a] pyrazine G-479. Bioorg Med Chem Lett. 2014 Oct 1;24(19):4714-4723. | ||||
REF 5 | Mechanism of MEK inhibition determines efficacy in mutant KRAS- versus BRAF-driven cancers. Nature. 2013 Sep 12;501(7466):232-6. | ||||
REF 6 | Fragment-Based Discovery of Novel Allosteric MEK1 Binders. ACS Med Chem Lett. 2021 Jan 27;12(2):302-308. | ||||
REF 7 | Disruption of CRAF-mediated MEK activation is required for effective MEK inhibition in KRAS mutant tumors. Cancer Cell. 2014 May 12;25(5):697-710. | ||||
REF 8 | 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 9 | Engineering human MEK-1 for structural studies: A case study of combinatorial domain hunting. J Struct Biol. 2012 Feb;177(2):329-34. |
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