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 T70977 Target Info
Target Name Glycogen synthase kinase-3 beta (GSK-3B)
Synonyms Serine/threonine-protein kinase GSK3B; GSK-3 beta
Target Type Clinical trial Target
Gene Name GSK3B
Biochemical Class Kinase
UniProt ID
GSK3B_HUMAN
Ligand General Information  Top
Ligand Name CHIR-99021 Ligand Info
Canonical SMILES CC1=CN=C(N1)C2=CN=C(N=C2C3=C(C=C(C=C3)Cl)Cl)NCCNC4=NC=C(C=C4)C#N
InChI 1S/C22H18Cl2N8/c1-13-10-29-21(31-13)17-12-30-22(32-20(17)16-4-3-15(23)8-18(16)24)27-7-6-26-19-5-2-14(9-25)11-28-19/h2-5,8,10-12H,6-7H2,1H3,(H,26,28)(H,29,31)(H,27,30,32)
InChIKey AQGNHMOJWBZFQQ-UHFFFAOYSA-N
PubChem Compound ID 9956119
Drug Binding Sites of Target  Top
PDB ID: 6B8J      Co-structure of human glycogen synthase kinase beta with a selective (5-imidazol-2-yl-4-phenylpyrimidin-2-yl)[2-(2-pyridylamino)ethyl]amine inhibitor
Method X-ray diffraction Resolution 2.60 Å Mutation No [1]
PDB Sequence
VTTVVATPGQ
46
GPDRPQEVSY
56
TDTKVIGNGS
66
FGVVYQAKLC
76
DSGELVAIKK
86

VLQDKRFKNR
96
ELQIMRKLDH
106
CNIVRLRYFF
116
YSSGDEVYLN
129
LVLDYVPETV
139

YRVARHYSRA
149
KQTLPVIYVK
159
LYMYQLFRSL
169
AYIHSFGICH
179
RDIKPQNLLL
189

DPDTAVLKLC
199
DFGSAKQLVR
209
GEPNVSICSR
220
YYRAPELIFG
230
ATDYTSSIDV
240

WSAGCVLAEL
250
LLGQPIFPGD
260
SGVDQLVEII
270
KVLGTPTREQ
280
IREMNPNYTE
290

FKFPQIKAHP
300
WTKVFRPRTP
310
PEAIALCSRL
320
LEYTPTARLT
330
PLEACAHSFF
340

DELRDPNVKL
350
PNGRDTPALF
360
NFTTQELSSN
370
PPLATILIPP
380
HARI
Residue
Distance (Å)
ILE62
3.385
GLY63
3.603
ASN64
3.491
PHE67
3.381
VAL70
3.665
ALA83
3.636
LYS85
4.740
VAL110
4.287
LEU132
3.441
ASP133
3.309
TYR134
3.270
Residue
Distance (Å)
VAL135
2.356
PRO136
3.925
GLU137
4.138
THR138
3.708
ARG141
3.448
GLN185
3.641
ASN186
4.321
LEU188
3.312
CYS199
3.806
ASP200
3.729
PDB ID: 5HLN      X-RAY CRYSTAL STRUCTURE OF GSK3B IN COMPLEX WITH CHIR99021
Method X-ray diffraction Resolution 3.10 Å Mutation No [2]
PDB Sequence
GSKVTTVVAT
43
PGQGPDRPQE
53
VSYTDTKVIG
63
NGSFGVVYQA
73
KLCDSGELVA
83

IKKVLQDKRF
93
KNRELQIMRK
103
LDHCNIVRLR
113
YFFYSSDEVY
127
LNLVLDYVPE
137

TVYRVARHYS
147
RAKQTLPVIY
157
VKLYMYQLFR
167
SLAYIHSFGI
177
CHRDIKPQNL
187

LLDPDTAVLK
197
LCDFGSAKQL
207
VRGEPNVSIC
218
SRYYRAPELI
228
FGATDYTSSI
238

DVWSAGCVLA
248
ELLLGQPIFP
258
GDSGVDQLVE
268
IIKVLGTPTR
278
EQIREMNPNY
288

TEFKFPQIKA
298
HPWTKVFRPR
308
TPPEAIALCS
318
RLLEYTPTAR
328
LTPLEACAHS
338

FFDELRDPNV
348
KLPNGRDTPA
358
LFNFTTQELS
368
SNPPLATILI
378
PPHARI
Residue
Distance (Å)
ILE62
3.583
GLY63
3.602
ASN64
3.540
PHE67
3.472
VAL70
3.784
ALA83
3.564
LYS85
4.234
VAL110
4.120
LEU132
3.785
ASP133
3.364
TYR134
3.400
Residue
Distance (Å)
VAL135
2.606
PRO136
3.480
GLU137
4.074
THR138
3.641
ARG141
3.840
GLN185
3.359
ASN186
4.261
LEU188
3.272
CYS199
3.469
ASP200
3.694
References  Top
REF 1 Synthesis, Binding Mode, and Antihyperglycemic Activity of Potent and Selective (5-Imidazol-2-yl-4-phenylpyrimidin-2-yl)[2-(2-pyridylamino)ethyl]amine Inhibitors of Glycogen Synthase Kinase 3. J Med Chem. 2017 Oct 26;60(20):8482-8514.
REF 2 Inhibitors of Glycogen Synthase Kinase 3 with Exquisite Kinome-Wide Selectivity and Their Functional Effects. ACS Chem Biol. 2016 Jul 15;11(7):1952-63.

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