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 T62449 Target Info
Target Name Checkpoint kinase-1 (CHK1)
Synonyms Serine/threonine-protein kinase Chk1; Chk1; Cell cycle checkpoint kinase; CHK1 checkpoint homolog
Target Type Clinical trial Target
Gene Name CHEK1
Biochemical Class Kinase
UniProt ID
CHK1_HUMAN
Ligand General Information  Top
Ligand Name Staurosporine Ligand Info
Canonical SMILES CC12C(C(CC(O1)N3C4=CC=CC=C4C5=C6C(=C7C8=CC=CC=C8N2C7=C53)CNC6=O)NC)OC
InChI 1S/C28H26N4O3/c1-28-26(34-3)17(29-2)12-20(35-28)31-18-10-6-4-8-14(18)22-23-16(13-30-27(23)33)21-15-9-5-7-11-19(15)32(28)25(21)24(22)31/h4-11,17,20,26,29H,12-13H2,1-3H3,(H,30,33)/t17-,20-,26-,28+/m1/s1
InChIKey HKSZLNNOFSGOKW-FYTWVXJKSA-N
PubChem Compound ID 44259
Drug Binding Sites of Target  Top
PDB ID: 7AKO      Crystal structure of CHK1 kinase domain in complex with a CLASPIN phosphopeptide
Method X-ray diffraction Resolution 1.80 Å Mutation Yes [1]
PDB Sequence
AVPFVEDWRL
11
VQTLGEGAYG
21
EVQLAVNRVT
31
EEAVAVKIVD
41
MKRAVDCPEN
51

IKKEICINKM
61
LNHENVVKFY
71
GHRREGNIQY
81
LFLEYCSGGE
91
LFDRIEPDIG
101

MPEPDAQRFF
111
HQLMAGVVYL
121
HGIGITHRDI
131
KPENLLLDER
141
DNLKISDFGL
151

ATVFRYNNRE
161
RLLNKMCGTL
171
PYVAPELLKR
181
REFHAEPVDV
191
WSCGIVLTAM
201

LAGELPWDQP
211
SDSCQEYSDW
221
KEKKTYLNPW
231
KKIDSAPLAL
241
LHKILVENPS
251

ARITIPDIKK
261
DRWYNKPLKK
271
Residue
Distance (Å)
LEU15
3.401
GLY16
3.665
GLU17
4.767
VAL23
3.745
ALA36
3.244
LYS38
4.353
VAL68
4.376
LEU84
3.777
GLU85
2.718
Residue
Distance (Å)
TYR86
3.442
CYS87
2.804
GLY90
3.793
GLU91
2.691
GLU134
2.822
ASN135
3.546
LEU137
3.250
SER147
3.114
ASP148
3.241
PDB ID: 5OOR      Structure of CHK1 10-pt. mutant complex with staurosporine
Method X-ray diffraction Resolution 1.90 Å Mutation Yes [2]
PDB Sequence
VPFVEDWDLV
12
QTLGEGAYGE
22
VQLAVNRVTE
32
EAVAVKIVDM
42
NIKKEICILK
60

MLNHENVIKF
70
YGHRREGNIQ
80
YLFMELASGG
90
SLFDRIEPDI
100
GMPEPDAQRF
110

FHQLMAGVVY
120
LHGIGITHRD
130
IKPHNLLLDE
140
RDNLKIADYS
150
LATVFRYNNR
160

ERLLNKMCGT
170
LPYVAPELLK
180
RREFHAEPVD
190
VWSCGIVLTA
200
MLAGELPWDQ
210

PSDSCQEYSD
220
WKEKKTYLNP
230
WKKIDSAPLA
240
LLHKILVENP
250
SARITIPDIK
260

KDRWYNKPLK
270
KGAKRPRVTS
280
GGV
Residue
Distance (Å)
LEU15
3.429
GLY16
3.548
GLU17
3.651
GLY18
4.881
VAL23
3.625
ALA36
3.323
LYS38
4.127
ILE68
4.015
MET84
3.518
GLU85
2.764
LEU86
3.408
Residue
Distance (Å)
ALA87
2.761
SER88
4.489
GLY89
4.960
GLY90
3.531
SER91
4.212
HIS134
2.937
ASN135
3.783
LEU137
3.252
ALA147
3.952
ASP148
3.307
PDB ID: 1NVR      The Complex Structure Of Checkpoint Kinase Chk1/Staurosporine
Method X-ray diffraction Resolution 1.80 Å Mutation No [3]
PDB Sequence
VPFVEDWDLV
12
QTLGEGAYGE
22
VQLAVNRVTE
32
EAVAVKIVDM
42
KNIKKEICIN
59

KMLNHENVVK
69
FYGHRREGNI
79
QYLFLEYCSG
89
GELFDRIEPD
99
IGMPEPDAQR
109

FFHQLMAGVV
119
YLHGIGITHR
129
DIKPENLLLD
139
ERDNLKISDF
149
GLATVFRYNN
159

RERLLNKMCG
169
TLPYVAPELL
179
KRREFHAEPV
189
DVWSCGIVLT
199
AMLAGELPWD
209

QPSDSCQEYS
219
DWKEKKTYLN
229
PWKKIDSAPL
239
ALLHKILVEN
249
PSARITIPDI
259

KKDRWYNKPL
269
KKGA
Residue
Distance (Å)
LEU15
3.340
GLY16
3.709
TYR20
3.037
VAL23
3.630
ALA36
3.379
LYS38
3.736
GLU55
4.119
VAL68
4.119
LEU84
3.850
GLU85
2.839
Residue
Distance (Å)
TYR86
3.456
CYS87
2.764
GLY90
3.757
GLU91
2.689
GLU134
2.915
ASN135
3.672
LEU137
3.284
SER147
3.047
ASP148
3.441
References  Top
REF 1 Structural basis for recruitment of the CHK1 DNA damage kinase by the CLASPIN scaffold protein. Structure. 2021 Jun 3;29(6):531-539.e3.
REF 2 Design of Leucine-Rich Repeat Kinase 2 (LRRK2) Inhibitors Using a Crystallographic Surrogate Derived from Checkpoint Kinase 1 (CHK1). J Med Chem. 2017 Nov 9;60(21):8945-8962.
REF 3 Structural basis for Chk1 inhibition by UCN-01. J Biol Chem. 2002 Nov 29;277(48):46609-15.

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