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 Lrrk2-IN-1 Ligand Info
Canonical SMILES CN1CCN(CC1)C2CCN(CC2)C(=O)C3=CC(=C(C=C3)NC4=NC=C5C(=N4)N(C6=CC=CC=C6C(=O)N5C)C)OC
InChI 1S/C31H38N8O3/c1-35-15-17-38(18-16-35)22-11-13-39(14-12-22)29(40)21-9-10-24(27(19-21)42-4)33-31-32-20-26-28(34-31)36(2)25-8-6-5-7-23(25)30(41)37(26)3/h5-10,19-20,22H,11-18H2,1-4H3,(H,32,33,34)
InChIKey IWMCPJZTADUIFX-UHFFFAOYSA-N
PubChem Compound ID 46843906
Drug Binding Sites of Target  Top
PDB ID: 5OQ5      Structure of CHK1 8-pt. mutant complex with aminopyrimido-benzodiazepinone LRRK2 inhibitor
Method X-ray diffraction Resolution 1.40 Å Mutation Yes [1]
PDB Sequence
VPFVEDWDLV
12
QTLGEGAYGE
22
VQLAVNRVTE
32
EAVAVKIVDM
42
KRCPENIKKE
55

ICILKMLNHE
65
NVIKFYGHRR
75
EGNIQYLFME
85
LASGGSLFDR
95
IEPDIGMPEP
105

DAQRFFHQLM
115
AGVVYLHGIG
125
ITHRDIKPHN
135
LLLDERDNLK
145
IADFGLATVF
155

RYNNRERLLN
165
KMCGTLPYVA
175
PELLKRREFH
185
AEPVDVWSCG
195
IVLTAMLAGE
205

LPWDQPSDSC
215
QEYSDWKEKK
225
TYLNPWKKID
235
SAPLALLHKI
245
LVENPSARIT
255

IPDIKKDRWY
265
NKPLK
Residue
Distance (Å)
LEU15
3.805
GLY16
4.014
VAL23
3.793
ALA36
3.732
ILE68
4.596
MET84
3.604
GLU85
3.570
LEU86
3.550
ALA87
2.913
Residue
Distance (Å)
SER88
3.523
GLY89
3.402
GLY90
3.792
ARG95
4.076
HIS134
3.467
ASN135
3.672
LEU137
3.594
ALA147
3.648
ASP148
3.927
PDB ID: 5OQ6      Structure of CHK1 12-pt. mutant complex with aminopyrimido-benzodiazepinone LRRK2 inhibitor
Method X-ray diffraction Resolution 1.95 Å Mutation Yes [1]
PDB Sequence
FVEDWDLVQT
14
LGEGSFGEVQ
24
LAVNRVTEEA
34
VAVKIVDNIK
53
KEICILKMLN
63

HENVIKFYGH
73
RREGNIQYLF
83
MELASGGSLF
93
DRIEPDIGMP
103
EPDAQRFFHQ
113

LMAGVVYLHG
123
IGITHRDIKP
133
HNLLLDERDN
143
LKIADYSLAT
153
VFRYNNRERL
163

LNKMCGTLPY
173
VAPELLKRRE
183
FHAEPVDVWS
193
CGIVLTAMLA
203
GELPWDQPSD
213

SCQEYSDWKE
223
KKTYLNPWKK
233
IDSAPLALLH
243
KILVENPSAR
253
ITIPDIKKDR
263

WYNKPLK
Residue
Distance (Å)
GLN13
4.275
THR14
3.409
LEU15
3.559
GLY16
4.025
VAL23
3.495
ALA36
3.849
ILE68
4.691
MET84
3.513
GLU85
3.591
LEU86
3.427
Residue
Distance (Å)
ALA87
2.895
SER88
3.483
GLY90
3.969
ASP94
4.921
HIS134
3.552
ASN135
3.383
LEU137
3.424
ALA147
3.601
ASP148
3.971
PDB ID: 5OOT      Structure of CHK1 10-pt. mutant complex with aminopyrimido-benzodiazepinone LRRK2 inhibitor
Method X-ray diffraction Resolution 2.10 Å Mutation Yes [1]
PDB Sequence
PFVEDWDLVQ
13
TLGEGAYGEV
23
QLAVNRVTEE
33
AVAVKIVDME
50
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
Residue
Distance (Å)
GLN13
3.658
THR14
3.466
LEU15
3.626
GLY16
4.007
VAL23
3.605
LEU25
4.913
ALA36
3.762
ILE68
4.921
MET84
3.560
GLU85
3.499
Residue
Distance (Å)
LEU86
3.517
ALA87
2.737
SER88
3.554
GLY89
4.981
GLY90
3.808
HIS134
3.587
ASN135
3.507
LEU137
3.528
ALA147
3.642
ASP148
4.038
References  Top
REF 1 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.

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