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 T35940 Target Info
Target Name 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
Target Type Clinical trial Target
Gene Name MAP2K1
Biochemical Class Kinase
UniProt ID
MP2K1_HUMAN
Ligand General Information  Top
Ligand Name PD-0325901 Ligand Info
Canonical SMILES C1=CC(=C(C=C1I)F)NC2=C(C=CC(=C2F)F)C(=O)NOCC(CO)O
InChI 1S/C16H14F3IN2O4/c17-11-3-2-10(16(25)22-26-7-9(24)6-23)15(14(11)19)21-13-4-1-8(20)5-12(13)18/h1-5,9,21,23-24H,6-7H2,(H,22,25)/t9-/m1/s1
InChIKey SUDAHWBOROXANE-SECBINFHSA-N
PubChem Compound ID 9826528
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
LEAFLTQKQK
59
VGELKDDDFE
69
KISELGAGNG
79
GVVFKVSHKP
89

SGLVMARKLI
99
HLEIKPAIRN
109
QIIRELQVLH
119
ECNSPYIVGF
129
YGAFYSDGEI
139

SICMEHMDGG
149
SLDQVLKKAG
159
RIPEQILGKV
169
SIAVIKGLTY
179
LREKHKIMHR
189

DVKPSNILVN
199
SRGEIKLCDF
209
GVSGQLIDAM
219
ANAFVGTRSY
229
MSPERLQGTH
239

YSVQSDIWSM
249
GLSLVEMAVG
259
RYPIPPPDAK
269
ELELMPMAIF
311
ELLDYIVNEP
321

PPKLPSGVFS
331
LEFQDFVNKC
341
LIKNPAERAD
351
LKQLMVHAFI
361
KRSDAEEVDF
371

AGWLCSTIGL
381
NQ
Residue
Distance (Å)
GLY77
3.727
ASN78
3.364
GLY79
3.085
GLY80
3.590
LYS97
3.084
ILE99
4.502
LEU115
3.194
LEU118
3.775
ILE126
4.822
VAL127
3.173
GLY128
4.292
PHE129
4.714
ILE141
3.447
Residue
Distance (Å)
MET143
3.730
ASP190
4.352
LEU206
4.966
CYS207
4.584
ASP208
3.197
PHE209
3.204
GLY210
3.694
VAL211
3.131
SER212
2.829
LEU215
3.581
ILE216
3.702
MET219
3.760
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
RLEAFLTQKQ
58
KVGELKDDDF
68
EKISELGAGN
78
GGVVFKVSHK
88

PSGLVMARKL
98
IHLEIKPAIR
108
NQIIRELQVL
118
HECNSPYIVG
128
FYGAFYSDGE
138

ISICMEHMDG
148
GSLDQVLKKA
158
GRIPEQILGK
168
VSIAVIKGLT
178
YLREKHKIMH
188

RDVKPSNILV
198
NSRGEIKLCD
208
FGVSGQLIDS
218
MANSFVGTRS
228
YMSPERLQGT
238

HYSVQSDIWS
248
MGLSLVEMAV
258
GRYPIPPPDA
268
KELELMFGCP
307
MAIFELLDYI
317

VNEPPPKLPS
327
GVFSLEFQDF
337
VNKCLIKNPA
347
ERADLKQLMV
357
HAFIKRSDAE
367

EVDFAGWLCS
377
TIGL
Residue
Distance (Å)
ALA76
4.935
GLY77
3.412
ASN78
4.280
GLY79
4.100
GLY80
3.351
VAL81
4.831
LYS97
2.778
ILE99
4.509
LEU115
3.886
LEU118
4.017
ILE126
4.843
VAL127
3.177
GLY128
4.754
PHE129
4.755
Residue
Distance (Å)
ILE141
3.377
MET143
4.009
ASP190
4.993
LEU206
4.848
CYS207
4.416
ASP208
3.449
PHE209
3.212
GLY210
3.391
VAL211
2.979
SER212
3.007
LEU215
3.763
ILE216
3.270
MET219
3.521
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 [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
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)
GLY77
3.606
ASN78
3.714
GLY79
3.441
GLY80
2.890
LYS97
2.741
ILE99
4.193
LEU115
3.321
LEU118
3.823
ILE126
4.954
VAL127
3.198
GLY128
4.452
PHE129
4.625
ILE141
3.352
Residue
Distance (Å)
MET143
3.647
ASP190
4.642
LEU206
4.889
CYS207
4.557
ASP208
3.125
PHE209
3.302
GLY210
3.633
VAL211
3.290
SER212
2.990
LEU215
3.548
ILE216
4.045
MET219
3.365
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 Crystal structures of MEK1 binary and ternary complexes with nucleotides and inhibitors. Biochemistry. 2009 Mar 31;48(12):2661-74.
REF 3 X-ray structure of the human mitogen-activated protein kinase kinase 1 (MEK1) in complex with an inhibitor and MgATP

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