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) : | 7° |
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
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
Uniprot | RGLGHGAFGEVYEVAVKTLDFLMEALIISKFNQNIVRCIGVFILLELMAGGDLKSFLREYLEENHFIHRDIAARNCLLIGDFGMA |
Structure: | RGLGHGAFGEVYEVAVKTLDFLMEALIISKFNQNIVRCIGVFILLELMAGGDLKSFLREYLEENHFIHRDIAARNCLLIGDFGMA |
Modified residues
No modified residues identified.
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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- LABELS
- KLIFS residue #
- Amino Acid
- None
- COLORS
- Interaction types
- KLIFS (all res.)
- KLIFS (interacting res.)
- None
- OTHER
- Show/hide non-interacting res.
- En/disable resizing interacting res.
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 | |||||||||||||||
■ |
Binding affinities
ChEMBL ID:CHEMBL2403108Bioaffinities: 125 records for 44 kinase(s)
Species | Kinase (ChEMBL naming) | Median | Min | Max | Type | Records |
---|---|---|---|---|---|---|
Homo sapiens | ALK tyrosine kinase receptor | 5.5 | 5.5 | 5.5 | pEC50 | 2 |
Homo sapiens | ALK tyrosine kinase receptor | 7.9 | 4 | 9.7 | pIC50 | 43 |
Homo sapiens | ALK tyrosine kinase receptor | 8.9 | 8.9 | 8.9 | pKd | 1 |
Homo sapiens | ALK tyrosine kinase receptor | 5.4 | 5.4 | 5.4 | pKi | 1 |
Homo sapiens | CaM kinase IV | 6.2 | 6.2 | 6.2 | pKd | 1 |
Homo sapiens | CaM-kinase kinase beta | 5.3 | 5.3 | 5.3 | pKd | 1 |
Homo sapiens | Cyclin-dependent kinase 2 | 5.4 | 5.4 | 5.4 | pIC50 | 1 |
Homo sapiens | Cyclin-dependent kinase 4 | 5.3 | 5.3 | 5.3 | pIC50 | 1 |
Homo sapiens | Dual specificty protein kinase CLK1 | 6 | 6 | 6 | pKd | 1 |
Homo sapiens | Epidermal growth factor receptor erbB1 | 5.6 | 5.5 | 5.6 | pEC50 | 4 |
Homo sapiens | Epidermal growth factor receptor erbB1 | 6.1 | 5.7 | 7.7 | pIC50 | 4 |
Homo sapiens | Fibroblast growth factor receptor 2 | 6.6 | 6.6 | 6.6 | pIC50 | 1 |
Homo sapiens | Fibroblast growth factor receptor 3 | 6.4 | 6.4 | 6.4 | pIC50 | 1 |
Homo sapiens | Fibroblast growth factor receptor 4 | 6 | 6 | 6 | pIC50 | 1 |
Homo sapiens | Focal adhesion kinase 1 | 6.7 | 6.7 | 6.7 | pKd | 1 |
Homo sapiens | Hepatocyte growth factor receptor | 5.9 | 5.5 | 6.6 | pIC50 | 3 |
Homo sapiens | Insulin-like growth factor I receptor | 6.4 | 6.4 | 8.1 | pIC50 | 2 |
Homo sapiens | Insulin-like growth factor I receptor | 4.7 | 4.7 | 4.7 | pKd | 1 |
Homo sapiens | Insulin receptor | 7 | 6.5 | 8.2 | pIC50 | 4 |
Homo sapiens | Insulin receptor | 5.4 | 5.4 | 5.4 | pKd | 1 |
Homo sapiens | MAP kinase signal-integrating kinase 2 | 5.7 | 5.7 | 5.7 | pIC50 | 1 |
Homo sapiens | Mitogen-activated protein kinase 7 | 5 | 5 | 5 | pKd | 1 |
Homo sapiens | Nerve growth factor receptor Trk-A | 5.6 | 5.6 | 5.6 | pIC50 | 1 |
Homo sapiens | Neurotrophic tyrosine kinase receptor type 2 | 5.7 | 5.7 | 5.7 | pIC50 | 1 |
Homo sapiens | Non-receptor tyrosine-protein kinase TNK1 | 7.6 | 7.6 | 7.6 | pKd | 1 |
Homo sapiens | Platelet-derived growth factor receptor alpha | 5.9 | 5.9 | 5.9 | pIC50 | 1 |
Homo sapiens | Protein tyrosine kinase 2 beta | 4.7 | 4.7 | 4.7 | pKd | 1 |
Homo sapiens | Proto-oncogene tyrosine-protein kinase ROS | 8.4 | 5.7 | 8.7 | pIC50 | 6 |
Homo sapiens | Proto-oncogene tyrosine-protein kinase ROS | 9.2 | 6.6 | 9.4 | pKi | 3 |
Homo sapiens | Rho-associated protein kinase 2 | 5.9 | 5.9 | 5.9 | pIC50 | 1 |
Homo sapiens | Ribosomal protein S6 kinase alpha 1 | 4.7 | 4.7 | 4.7 | pKd | 2 |
Homo sapiens | Serine/threonine-protein kinase PLK4 | 5.2 | 5.2 | 5.2 | pKd | 1 |
Homo sapiens | Stem cell growth factor receptor | 5.5 | 5.5 | 5.9 | pIC50 | 2 |
Homo sapiens | Testis-specific serine/threonine-protein kinase 1 | 7.6 | 7.6 | 7.6 | pIC50 | 1 |
Homo sapiens | Tyrosine kinase non-receptor protein 2 | 6 | 6 | 6 | pKd | 1 |
Homo sapiens | Tyrosine-protein kinase ABL | 5.9 | 5.9 | 5.9 | pIC50 | 1 |
Homo sapiens | Tyrosine-protein kinase BTK | 5.5 | 5.5 | 5.5 | pIC50 | 1 |
Homo sapiens | Tyrosine-protein kinase FER | 6.7 | 6.7 | 6.7 | pKd | 1 |
Homo sapiens | Tyrosine-protein kinase FES | 5.8 | 5.8 | 5.8 | pKd | 1 |
Homo sapiens | Tyrosine-protein kinase FGR | 5.7 | 5.7 | 5.7 | pIC50 | 1 |
Homo sapiens | Tyrosine-protein kinase JAK1 | 5.4 | 5.4 | 5.4 | pIC50 | 2 |
Homo sapiens | Tyrosine-protein kinase JAK2 | 5.7 | 5.7 | 6.2 | pIC50 | 4 |
Homo sapiens | Tyrosine-protein kinase JAK3 | 5.1 | 5.1 | 5.1 | pIC50 | 2 |
Homo sapiens | Tyrosine-protein kinase LCK | 6.2 | 6.2 | 6.3 | pIC50 | 2 |
Homo sapiens | Tyrosine-protein kinase Lyn | 5.6 | 5.6 | 6.1 | pIC50 | 2 |
Homo sapiens | Tyrosine-protein kinase receptor FLT3 | 5.5 | 5.5 | 7.2 | pIC50 | 2 |
Homo sapiens | Tyrosine-protein kinase receptor FLT3 | 5.4 | 5.4 | 5.4 | pKd | 1 |
Homo sapiens | Tyrosine-protein kinase receptor RET | 5.6 | 5.6 | 6.4 | pIC50 | 2 |
Homo sapiens | Tyrosine-protein kinase SRC | 5.8 | 5.8 | 5.8 | pIC50 | 1 |
Homo sapiens | Tyrosine-protein kinase SYK | 5.5 | 5.5 | 5.5 | pIC50 | 1 |
Homo sapiens | Tyrosine-protein kinase ZAP-70 | 5 | 5 | 5 | pIC50 | 1 |
Homo sapiens | Vascular endothelial growth factor receptor 2 | 5.4 | 5.4 | 5.4 | pIC50 | 1 |