Target Binding Site Detail

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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 Selumetinib Ligand Info
Canonical SMILES CN1C=NC2=C1C=C(C(=C2F)NC3=C(C=C(C=C3)Br)Cl)C(=O)NOCCO
InChI 1S/C17H15BrClFN4O3/c1-24-8-21-16-13(24)7-10(17(26)23-27-5-4-25)15(14(16)20)22-12-3-2-9(18)6-11(12)19/h2-3,6-8,22,25H,4-5H2,1H3,(H,23,26)
InChIKey CYOHGALHFOKKQC-UHFFFAOYSA-N
PubChem Compound ID 10127622
Drug Binding Sites of Target  Top
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
AFLTQKQKVG
61
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
SGQLIDAMAN
221
AFVGTRSYMS
231
PERLQGTHYS
241

VQSDIWSMGL
251
SLVEMAVGRY
261
PIPPPDAKEL
271
ELMPMAIFEL
313
LDYIVNEPPP
323

KLPSGVFSLE
333
FQDFVNKCLI
343
KNPAERADLK
353
QLMVHAFIKR
363
SDAEEVDFAG
373

WLCSTIGLNQ
383
Residue
Distance (Å)
GLY79
2.707
GLY80
3.954
LYS97
3.569
ILE99
3.865
LEU115
3.386
LEU118
3.843
ILE126
4.389
VAL127
3.385
GLY128
4.667
PHE129
4.780
ILE141
3.703
MET143
3.648
Residue
Distance (Å)
LEU206
4.860
CYS207
4.132
ASP208
3.059
PHE209
3.348
GLY210
3.353
VAL211
3.107
SER212
2.863
GLY213
4.892
LEU215
3.568
ILE216
3.372
MET219
3.420
PDB ID: 4U7Z      Mitogen-Activated Protein Kinase Kinase (MEK1) bound to G805
Method X-ray diffraction Resolution 2.81 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
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)
GLY77
3.750
ASN78
3.543
GLY79
4.089
GLY80
3.590
LYS97
3.078
ILE99
4.268
LEU115
3.295
LEU118
3.704
ILE126
4.759
VAL127
3.274
GLY128
4.733
ILE141
3.634
Residue
Distance (Å)
MET143
3.463
ASP190
4.523
LEU206
4.739
CYS207
4.375
ASP208
3.323
PHE209
3.227
GLY210
3.441
VAL211
2.934
SER212
3.129
LEU215
3.461
ILE216
3.842
MET219
4.536
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 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.

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