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 | adenosine diphosphate | Ligand Info | |||
| Canonical SMILES | C1=NC(=C2C(=N1)N(C=N2)C3C(C(C(O3)COP(=O)(O)OP(=O)(O)O)O)O)N | ||||
| InChI | 1S/C10H15N5O10P2/c11-8-5-9(13-2-12-8)15(3-14-5)10-7(17)6(16)4(24-10)1-23-27(21,22)25-26(18,19)20/h2-4,6-7,10,16-17H,1H2,(H,21,22)(H2,11,12,13)(H2,18,19,20)/t4-,6-,7-,10-/m1/s1 | ||||
| InChIKey | XTWYTFMLZFPYCI-KQYNXXCUSA-N | ||||
| PubChem Compound ID | 6022 | ||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| PDB ID: 6NYB Structure of a MAPK pathway complex | ||||||
| Method | Electron microscopy | Resolution | 4.10 Å | Mutation | Yes | [1] |
| PDB Sequence |
QKQKVGELKD
65 DDFEKISELG75 AGNGGVVFKV85 SHKPSGLVMA95 RKLIHLEIKP105 AIRNQIIREL 115 QVLHECNSPY125 IVGFYGAFYS135 DGEISICMEH145 MDGGSLDQVL155 KKAGRIPEQI 165 LGKVSIAVIK175 GLTYLREKHK185 IMHRDVKPSN195 ILVNSRGEIK205 LCDFGVSGQL 215 IDAMANAFVG225 TRSYMSPERL235 QGTHYSVQSD245 IWSMGLSLVE255 MAVGRYPIPP 265 PDPMAIFELL314 DYIVNEPPPK324 LPSGVFSLEF334 QDFVNKCLIK344 NPAERADLKQ 354 LMVHAFIKRS364 DAEEVDFAGW374 LCSTIGLNQ
|
|||||
|
|
LEU74
3.432
GLY75
3.733
ALA76
3.621
GLY77
3.668
ASN78
4.247
GLY79
4.690
GLY80
3.616
VAL81
4.923
VAL82
3.191
ALA95
3.529
LYS97
2.746
VAL127
4.891
|
|||||
| PDB ID: 3EQI X-ray structure of the human mitogen-activated protein kinase kinase 1 (MEK1) in a binary complex with ADP and MG2P | ||||||
| Method | X-ray diffraction | Resolution | 1.90 Å | Mutation | Yes | [2] |
| PDB Sequence |
ELELDEQQRK
48 RLEAFLTQKQ58 KVGELKDDDF68 EKISELGAGN78 GGVVFKVSHK88 PSGLVMARKL 98 IHLEIKPAIR108 NQIIRELQVL118 HECNSPYIVG128 FYGAFYSDGE138 ISICMEHMDG 148 GSLDQVLKKA158 GRIPEQILGK168 VSIAVIKGLT178 YLREKHKIMH188 RDVKPSNILV 198 NSRGEIKLCD208 FGVSGQLIDS218 MANSFVGTRS228 YMSPERLQGT238 HYSVQSDIWS 248 MGLSLVEMAV258 GRYPIPPPDA268 KELELMFGCP307 MAIFELLDYI317 VNEPPPKLPS 327 GVFSLEFQDF337 VNKCLIKNPA347 ERADLKQLMV357 HAFIKRSDAE367 EVDFAGWLCS 377 TIGLN
|
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|
|
LEU74
3.455
GLY75
3.667
ALA76
3.076
GLY77
4.076
GLY80
3.311
VAL81
4.903
VAL82
3.561
ALA95
3.429
LYS97
2.782
VAL127
3.881
MET143
3.747
GLU144
2.734
|
|||||
| PDB ID: 3EQH X-ray structure of the human mitogen-activated protein kinase kinase 1 (MEK1) in a ternary complex with U0126, ADP and MG2P | ||||||
| Method | X-ray diffraction | Resolution | 2.00 Å | Mutation | Yes | [2] |
| PDB Sequence |
ELELDEQQRK
48 RLEAFLTQKQ58 KVGELKDDDF68 EKISELGAGN78 GGVVFKVSHK88 PSGLVMARKL 98 IHLEIKPAIR108 NQIIRELQVL118 HECNSPYIVG128 FYGAFYSDGE138 ISICMEHMDG 148 GSLDQVLKKA158 GRIPEQILGK168 VSIAVIKGLT178 YLREKHKIMH188 RDVKPSNILV 198 NSRGEIKLCD208 FGVSGQLIDS218 MANSFVGTRS228 YMSPERLQGT238 HYSVQSDIWS 248 MGLSLVEMAV258 GRYPIPPPDA268 KELELMFGCP307 MAIFELLDYI317 VNEPPPKLPS 327 GVFSLEFQDF337 VNKCLIKNPA347 ERADLKQLMV357 HAFIKRSDAE367 EVDFAGWLCS 377 TIGL
|
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|
|
LEU74
3.727
GLY75
3.895
ALA76
3.563
GLY77
3.683
GLY80
3.381
VAL82
3.586
ALA95
3.367
LYS97
3.230
VAL127
4.227
MET143
4.249
GLU144
2.858
HIS145
3.883
|
|||||
| PDB ID: 3EQG X-ray structure of the human mitogen-activated protein kinase kinase 1 (MEK1) in a ternary complex with PD, ADP AND MG2P | ||||||
| Method | X-ray diffraction | Resolution | 2.50 Å | Mutation | Yes | [2] |
| PDB Sequence |
ELELDEQQRK
48 RLEAFLTQKQ58 KVGELKDDDF68 EKISELGAGN78 GGVVFKVSHK88 PSGLVMARKL 98 IHLEIKPAIR108 NQIIRELQVL118 HECNSPYIVG128 FYGAFYSDGE138 ISICMEHMDG 148 GSLDQVLKKA158 GRIPEQILGK168 VSIAVIKGLT178 YLREKHKIMH188 RDVKPSNILV 198 NSRGEIKLCD208 FGVSGQLIDS218 MANSFVGTRS228 YMSPERLQGT238 HYSVQSDIWS 248 MGLSLVEMAV258 GRYPIPPPDA268 KELELMFGCP307 MAIFELLDYI317 VNEPPPKLPS 327 GVFSLEFQDF337 VNKCLIKNPA347 ERADLKQLMV357 HAFIKRSDAE367 EVDFAGWLCS 377 TIGL
|
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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 .ADP or .ADP2 or .ADP3 or :3ADP;style chemicals stick;color identity;select .A:74 or .A:75 or .A:76 or .A:77 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: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
3.495
GLY75
3.759
ALA76
3.718
GLY77
3.819
GLY80
4.024
VAL82
3.731
ALA95
3.525
LYS97
3.136
VAL127
4.173
MET143
3.157
GLU144
3.039
HIS145
4.155
|
|||||
| PDB ID: 4ARK CRYSTAL STRUCTURE OF THE CATALYTIC DOMAIN OF HUMAN MAP KINASE KINASE 1 (MEK1) IN COMPLEX WITH A SMALL MOLECULE INHIBITOR AND ADP | ||||||
| Method | X-ray diffraction | Resolution | 2.60 Å | Mutation | No | [3] |
| 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 LELMFPMAIF311 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 .ADP or .ADP2 or .ADP3 or :3ADP;style chemicals stick;color identity;select .A:74 or .A:75 or .A:76 or .A:77 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: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
3.783
GLY75
4.033
ALA76
3.975
GLY77
3.349
GLY80
3.420
VAL81
4.750
VAL82
2.949
ALA95
3.572
LYS97
3.018
VAL127
4.260
MET143
3.374
GLU144
3.063
|
|||||
| PDB ID: 3MBL Crystal Structure of the human mitogen-activated protein kinase kinase 1 (MEK 1) in complex with ligand and MgADP | ||||||
| Method | X-ray diffraction | Resolution | 2.60 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 NSFVGTRSYM230 SPERLQGTHY240 SVQSDIWSMG250 LSLVEMAVGR260 YPIPPPDAKE 270 LELMFPMAIF311 ELLDYIVNEP321 PPKLPSGVFS331 LEFQDFVNKC341 LIKNPAERAD 351 LKQLMVHAFI361 KRSDAEEVDF371 AGWLCSTIGL381
|
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .ADP or .ADP2 or .ADP3 or :3ADP;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: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
3.788
GLY75
3.646
ALA76
3.641
GLY77
3.466
ASN78
4.924
GLY80
3.317
VAL82
3.910
ALA95
3.359
LYS97
2.547
VAL127
4.388
MET143
2.681
GLU144
3.063
|
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| References | Top | ||||
|---|---|---|---|---|---|
| REF 1 | Architecture of autoinhibited and active BRAF-MEK1-14-3-3 complexes. Nature. 2019 Nov;575(7783):545-550. | ||||
| REF 2 | Crystal structures of MEK1 binary and ternary complexes with nucleotides and inhibitors. Biochemistry. 2009 Mar 31;48(12):2661-74. | ||||
| REF 3 | Optimization of allosteric MEK inhibitors. Part 1: Venturing into underexplored SAR territories. Bioorg Med Chem Lett. 2013 Apr 15;23(8):2384-90. | ||||
| REF 4 | Structure-based design and synthesis of pyrrole derivatives as MEK inhibitors. Bioorg Med Chem Lett. 2010 Jul 15;20(14):4156-8. | ||||
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