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 T00749 Target Info
Target Name MEK kinase kinase 1 (MAP4K1)
Synonyms Mitogen-activated protein kinase kinase kinase kinase 1; MEKKK 1; MAPK/ERK kinase kinase kinase 1; Hematopoietic progenitor kinase; HPK1
Target Type Clinical trial Target
Gene Name MAP4K1
Biochemical Class Kinase
UniProt ID
M4K1_HUMAN
Ligand General Information  Top
Ligand Name Sunitinib Ligand Info
Canonical SMILES CCN(CC)CCNC(=O)C1=C(NC(=C1C)C=C2C3=C(C=CC(=C3)F)NC2=O)C
InChI 1S/C22H27FN4O2/c1-5-27(6-2)10-9-24-22(29)20-13(3)19(25-14(20)4)12-17-16-11-15(23)7-8-18(16)26-21(17)28/h7-8,11-12,25H,5-6,9-10H2,1-4H3,(H,24,29)(H,26,28)/b17-12-
InChIKey WINHZLLDWRZWRT-ATVHPVEESA-N
PubChem Compound ID 5329102
Drug Binding Sites of Target  Top
PDB ID: 6NG0      Crystal structure of HPK1 kinase domain T165E,S171E phosphomimetic mutant in complex with sunitinib in the inactive state.
Method X-ray diffraction Resolution 2.05 Å Mutation Yes [1]
PDB Sequence
PDIFNRDPRD
15
HYDLLQRLGG
25
GEVFKARDKV
38
SGDLVALKMV
48
KMEPDDDVST
58

LQKEILILKT
68
CRHANIVAYH
78
GSYLWLQKLW
88
ICMEFCGAGS
98
LQDIYQVTGS
108

LSELQISYVC
118
REVLQGLAYL
128
HSQKKIHRDI
138
KGANILINDA
148
GEVRLADFGI
158

SALARRLEFI
173
GTPYWMAPEV
183
AAVALKGGYN
193
ELCDIWSLGI
203
TAIELAELQP
213

PLFDVHPLRV
223
LFLMTKSGYQ
233
PPRLKEKGKW
243
SAAFHNFIKV
253
TLTKSPKKRP
263

SATKMLSHQL
273
VSQPGLNRGL
283
ILDLLDKLKN
293
PGKGPSIGD
Residue
Distance (Å)
GLN21
3.761
ARG22
4.111
LEU23
3.270
GLY24
4.474
VAL31
4.001
ALA44
3.380
LYS46
3.831
VAL75
4.075
MET91
3.551
GLU92
2.931
Residue
Distance (Å)
PHE93
3.663
CYS94
2.727
GLY95
3.322
ALA96
4.473
GLY97
3.548
SER98
4.829
ASP101
2.974
LEU144
3.486
ALA154
3.548
ASP155
3.097
PDB ID: 6NFZ      Crystal structure of diphosphorylated HPK1 kinase domain in complex with sunitinib in the active state.
Method X-ray diffraction Resolution 2.97 Å Mutation No [1]
PDB Sequence
DIFNRDPRDH
16
YDLLQRLGTY
28
GEVFKARDKV
38
SGDLVALKMV
48
TLQKEILILK
67

TCRHANIVAY
77
HGSYLWICME
92
FCGAGSLQDI
102
YQVTGSLSEL
112
QISYVCREVL
122

QGLAYLHSQK
132
KIHRDIKGAN
142
ILINDAGEVR
152
LADFGISAQI
162
GALARRLFIG
174

TPYWMAPEVA
184
AVALKGGYNE
194
LCDIWSLGIT
204
AIELAELQPP
214
LFDVHPLRVL
224

FLMTKSGYQP
234
PRLKEKGKWS
244
AAFHNFIKVT
254
LTKSPKKRPS
264
ATKMLSHQLV
274

SQPGLNRGLI
284
LDLLDKLK
Residue
Distance (Å)
GLN21
4.822
LEU23
2.158
GLY24
2.247
THR27
3.734
VAL31
2.314
LYS33
3.867
ALA44
3.046
LEU66
4.680
VAL75
2.486
MET91
2.628
GLU92
2.315
PHE93
2.682
CYS94
2.176
Residue
Distance (Å)
GLY95
2.479
ALA96
3.733
GLY97
2.535
SER98
3.320
ASP101
1.312
ILE102
3.297
GLN104
4.194
VAL105
2.942
LEU144
2.808
ALA154
2.881
ASP155
3.405
LEU291
2.823
PDB ID: 6NFY      Crystal structure of nonphosphorylated, HPK1 kinase domain in complex with sunitinib in the inactive state.
Method X-ray diffraction Resolution 2.17 Å Mutation No [1]
PDB Sequence
GSNRDPRDHY
17
DLLQRLGGGE
30
VFKARDKVSG
40
DLVALKMVKM
50
EPDDDVSTLQ
60

KEILILKTCR
70
HANIVAYHGS
80
YLWLQKLWIC
90
MEFCGAGSLQ
100
DIYQVTGSLS
110

ELQISYVCRE
120
VLQGLAYLHS
130
QKKIHRDIKG
140
ANILINDAGE
150
VRLADFGISA
160

QIGATLARRL
170
SFIGTPYWMA
180
PEVAAVALKG
190
GYNELCDIWS
200
LGITAIELAE
210

LQPPLFDVHP
220
LRVLFLMTKS
230
GYQPPRLKEK
240
GKWSAAFHNF
250
IKVTLTKSPK
260

KRPSATKMLS
270
HQLVSQPGLN
280
RGLILDLLDK
290
LK
Residue
Distance (Å)
LEU23
3.650
GLY24
4.548
VAL31
4.349
ALA44
3.367
LYS46
3.415
VAL75
3.864
MET91
3.991
GLU92
2.831
PHE93
3.580
Residue
Distance (Å)
CYS94
2.799
GLY95
3.199
ALA96
4.417
GLY97
3.690
ASP101
3.340
VAL105
4.493
LEU144
3.401
ALA154
3.685
References  Top
REF 1 Multiple conformational states of the HPK1 kinase domain in complex with sunitinib reveal the structural changes accompanying HPK1 trans-regulation. J Biol Chem. 2019 Jun 7;294(23):9029-9036.

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