4MKC - chain A (model B) | Anaplastic lymphoma receptor tyrosine kinase
Structure information
PDB:4MKC
PubMed:24675041
Release date:2014-04-09
Resolution:2.01 Å
 
Kinase:ALK
Family:ALK
Group:TK
Species:HUMAN
 
Quality Score:8
Missing Residues:0
Missing Atoms:0
DFG conformation:in
αC-helix conformation:in
Salt bridge KIII.17 and EαC.24:Yes (2.9Å)
 
 
ASP rotation (xDFG.81) :
PHE rotation (xDFG.82) :17°
Activation loop position:-4.5Å
αC-helix position:17.6Å
 
G-rich loop angle:60.8°
G-rich loop distance:17.8Å
G-rich loop rotation:89.3°
Other models from this PDB:
2D & 3D views

The orthosteric binding pocket
Binding pocket waters
The following waters were found in the defined clusters:
I2
H-bond protein
I4
H-bond protein
I5
H-bond protein
Binding pocket sequence
UniprotRGLGHGAFGEVYEVAVKTLDFLMEALIISKFNQNIVRCIGVFILLELMAGGDLKSFLREYLEENHFIHRDIAARNCLLIGDFGMA
Structure:RGLGHGAFGEVYEVAVKTLDFLMEALIISKFNQNIVRCIGVFILLELMAGGDLKSFLREYLEENHFIHRDIAARNCLLIGDFGMA


Modified residues
No modified residues identified.
Orthosteric ligand
2D structure of the orthosteric ligand
Ligand HET-code: 4MK
Ligand Name: 5-chloro-N~2~-[5-methyl-4-(piperidin-4-yl)-2-(propan-2-yloxy)phenyl]-N~4~-[2-(propan-2-ylsulfonyl)phenyl]pyrimidine-2,4-diamine

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  • KLIFS residue #
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This ligand targets the following (sub)pockets:
Main pockets
Front

Gate

Back

Subpockets
FP-I

FP-II

BP-I-A

BP-I-B

BP-II-in

BP-II-A-in

BP-II-B-in

BP-II-out

BP-II-B

BP-III

BP-IV

BP-V

Kinase-ligand interactions
Hydrophobic Aromatic face-to-face Aromatic face-to-edge H-bond donor H-bond acceptor Ionic positive Ionic negative
I g.l II III αC
1 R
1120
2 G
1121
3 L
1122
4 G
1123
5 H
1124
6 G
1125
7 A
1126
8 F
1127
9 G
1128
10 E
1129
11 V
1130
12 Y
1131
13 E
1132
14 V
1147
15 A
1148
16 V
1149
17 K
1150
18 T
1151
19 L
1152
20 D
1163
αC b.l IV
21 F
1164
22 L
1165
23 M
1166
24 E
1167
25 A
1168
26 L
1169
27 I
1170
28 I
1171
29 S
1172
30 K
1173
31 F
1174
32 N
1175
33 Q
1177
34 N
1178
35 I
1179
36 V
1180
37 R
1181
38 C
1182
39 I
1183
40 G
1184
IV V GK hinge linker αD αE
41 V
1185
42 F
1193
43 I
1194
44 L
1195
45 L
1196
46 E
1197
47 L
1198
48 M
1199
49 A
1200
50 G
1201
51 G
1202
52 D
1203
53 L
1204
54 K
1205
55 S
1206
56 F
1207
57 L
1208
58 R
1209
59 E
1210
60 Y
1239
αE VI c.l VII VIII x
61 L
1240
62 E
1241
63 E
1242
64 N
1243
65 H
1244
66 F
1245
67 I
1246
68 H
1247
69 R
1248
70 D
1249
71 I
1250
72 A
1251
73 A
1252
74 R
1253
75 N
1254
76 C
1255
77 L
1256
78 L
1257
79 I
1268
80 G
1269
DFG a.l
81 D
1270
82 F
1271
83 G
1272
84 M
1273
85 A
1274

Interaction pattern search
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Binding affinities
ChEMBL ID:CHEMBL2403108
Bioaffinities: 125 records for 44 kinase(s)

Species Kinase (ChEMBL naming) Median Min Max Type Records
Homo sapiensALK tyrosine kinase receptor5.55.55.5pEC502
Homo sapiensALK tyrosine kinase receptor7.949.7pIC5043
Homo sapiensALK tyrosine kinase receptor8.98.98.9pKd1
Homo sapiensALK tyrosine kinase receptor5.45.45.4pKi1
Homo sapiensCaM kinase IV6.26.26.2pKd1
Homo sapiensCaM-kinase kinase beta5.35.35.3pKd1
Homo sapiensCyclin-dependent kinase 25.45.45.4pIC501
Homo sapiensCyclin-dependent kinase 45.35.35.3pIC501
Homo sapiensDual specificty protein kinase CLK1666pKd1
Homo sapiensEpidermal growth factor receptor erbB15.65.55.6pEC504
Homo sapiensEpidermal growth factor receptor erbB16.15.77.7pIC504
Homo sapiensFibroblast growth factor receptor 26.66.66.6pIC501
Homo sapiensFibroblast growth factor receptor 36.46.46.4pIC501
Homo sapiensFibroblast growth factor receptor 4666pIC501
Homo sapiensFocal adhesion kinase 16.76.76.7pKd1
Homo sapiensHepatocyte growth factor receptor5.95.56.6pIC503
Homo sapiensInsulin-like growth factor I receptor6.46.48.1pIC502
Homo sapiensInsulin-like growth factor I receptor4.74.74.7pKd1
Homo sapiensInsulin receptor76.58.2pIC504
Homo sapiensInsulin receptor5.45.45.4pKd1
Homo sapiensMAP kinase signal-integrating kinase 25.75.75.7pIC501
Homo sapiensMitogen-activated protein kinase 7555pKd1
Homo sapiensNerve growth factor receptor Trk-A5.65.65.6pIC501
Homo sapiensNeurotrophic tyrosine kinase receptor type 25.75.75.7pIC501
Homo sapiensNon-receptor tyrosine-protein kinase TNK17.67.67.6pKd1
Homo sapiensPlatelet-derived growth factor receptor alpha5.95.95.9pIC501
Homo sapiensProtein tyrosine kinase 2 beta4.74.74.7pKd1
Homo sapiensProto-oncogene tyrosine-protein kinase ROS8.45.78.7pIC506
Homo sapiensProto-oncogene tyrosine-protein kinase ROS9.26.69.4pKi3
Homo sapiensRho-associated protein kinase 25.95.95.9pIC501
Homo sapiensRibosomal protein S6 kinase alpha 14.74.74.7pKd2
Homo sapiensSerine/threonine-protein kinase PLK45.25.25.2pKd1
Homo sapiensStem cell growth factor receptor5.55.55.9pIC502
Homo sapiensTestis-specific serine/threonine-protein kinase 17.67.67.6pIC501
Homo sapiensTyrosine kinase non-receptor protein 2666pKd1
Homo sapiensTyrosine-protein kinase ABL5.95.95.9pIC501
Homo sapiensTyrosine-protein kinase BTK5.55.55.5pIC501
Homo sapiensTyrosine-protein kinase FER6.76.76.7pKd1
Homo sapiensTyrosine-protein kinase FES5.85.85.8pKd1
Homo sapiensTyrosine-protein kinase FGR5.75.75.7pIC501
Homo sapiensTyrosine-protein kinase JAK15.45.45.4pIC502
Homo sapiensTyrosine-protein kinase JAK25.75.76.2pIC504
Homo sapiensTyrosine-protein kinase JAK35.15.15.1pIC502
Homo sapiensTyrosine-protein kinase LCK6.26.26.3pIC502
Homo sapiensTyrosine-protein kinase Lyn5.65.66.1pIC502
Homo sapiensTyrosine-protein kinase receptor FLT35.55.57.2pIC502
Homo sapiensTyrosine-protein kinase receptor FLT35.45.45.4pKd1
Homo sapiensTyrosine-protein kinase receptor RET5.65.66.4pIC502
Homo sapiensTyrosine-protein kinase SRC5.85.85.8pIC501
Homo sapiensTyrosine-protein kinase SYK5.55.55.5pIC501
Homo sapiensTyrosine-protein kinase ZAP-70555pIC501
Homo sapiensVascular endothelial growth factor receptor 25.45.45.4pIC501