2H8H - chain A (model B) | SRC proto-oncogene, non-receptor tyrosine kinase
Structure information
PDB: | 2H8H |
PubMed: | 17064066 |
Release date: | 2006-11-21 |
Resolution: | 2.2 Å |
Kinase: | SRC |
Family: | Src |
Group: | TK |
Species: | HUMAN |
Quality Score: | 8 |
Missing Residues: | 0 |
Missing Atoms: | 0 |
DFG conformation: | in |
αC-helix conformation: | out |
Salt bridge KIII.17 and EαC.24: | No (13.6Å) |
ASP rotation (xDFG.81) : | 334° |
PHE rotation (xDFG.82) : | 329° |
Activation loop position: | -4.5Å |
αC-helix position: | 21.2Å |
G-rich loop angle: | 53.4° |
G-rich loop distance: | 16.3Å |
G-rich loop rotation: | 46.1° |
Other models from this PDB:
2D & 3D views
Binding pocket waters
The following waters were found in the defined clusters:
I1
H-bond protein
I5
H-bond protein
I6
H-bond ligand
H-bond protein
Binding pocket sequence
Uniprot | VKLGQGCFGEVWMVAIKTLAFLQEAQVMKKLREKLVQLYAVYIVTEYMSKGSLLDFLKGYVERMNYVHRDLRAANILVVADFGLA |
Structure: | VKLGQGCFGEVWMVAIKTLAFLQEAQVMKKLREKLVQLYAVYIVTEYMSKGSLLDFLKGYVERMNYVHRDLRAANILVVADFGLA |
Modified residues
Residue 527 (not in pocket)
Phosphorylated tyrosine
Orthosteric ligand
Ligand HET-code: H8H
Ligand Name: N-(5-CHLORO-1,3-BENZODIOXOL-4-YL)-7-[2-(4-METHYLPIPERAZIN-1-YL)ETHOXY]-5-(TETRAHYDRO-2H-PYRAN-4-YLOXY)QUINAZOLIN-4-AMINE
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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 V 271 | 2 K 272 | 3 L 273 | 4 G 274 | 5 Q 275 | 6 G 276 | 7 C 277 | 8 F 278 | 9 G 279 | 10 E 280 | 11 V 281 | 12 W 282 | 13 M 283 | 14 V 292 | 15 A 293 | 16 I 294 | 17 K 295 | 18 T 296 | 19 L 297 | 20 A 306 |
■ | ■ | ■ | ■ | ■ | ■ | ||||||||||||||
αC | b.l | IV | |||||||||||||||||
21 F 307 | 22 L 308 | 23 Q 309 | 24 E 310 | 25 A 311 | 26 Q 312 | 27 V 313 | 28 M 314 | 29 K 315 | 30 K 316 | 31 L 317 | 32 R 318 | 33 E 320 | 34 K 321 | 35 L 322 | 36 V 323 | 37 Q 324 | 38 L 325 | 39 Y 326 | 40 A 327 |
IV | V | GK | hinge | linker | αD | αE | |||||||||||||
41 V 328 | 42 Y 335 | 43 I 336 | 44 V 337 | 45 T 338 | 46 E 339 | 47 Y 340 | 48 M 341 | 49 S 342 | 50 K 343 | 51 G 344 | 52 S 345 | 53 L 346 | 54 L 347 | 55 D 348 | 56 F 349 | 57 L 350 | 58 K 351 | 59 G 352 | 60 Y 376 |
■ | ■ | ■♦ | ■▲ | ■ | ■ | ■ | ■ | ||||||||||||
αE | VI | c.l | VII | VIII | x | ||||||||||||||
61 V 377 | 62 E 378 | 63 R 379 | 64 M 380 | 65 N 381 | 66 Y 382 | 67 V 383 | 68 H 384 | 69 R 385 | 70 D 386 | 71 L 387 | 72 R 388 | 73 A 389 | 74 A 390 | 75 N 391 | 76 I 392 | 77 L 393 | 78 V 394 | 79 V 402 | 80 A 403 |
■ | ■ | ||||||||||||||||||
DFG | a.l | ||||||||||||||||||
81 D 404 | 82 F 405 | 83 G 406 | 84 L 407 | 85 A 408 | |||||||||||||||
■ |
Binding affinities
ChEMBL ID:CHEMBL217092Bioaffinities: 83 records for 51 kinase(s)
Species | Kinase (ChEMBL naming) | Median | Min | Max | Type | Records |
---|---|---|---|---|---|---|
Homo sapiens | Activin receptor type-1 | 8.4 | 8.4 | 8.4 | pKd | 1 |
Homo sapiens | Activin receptor type-1B | 6.9 | 6.9 | 6.9 | pKd | 1 |
Homo sapiens | Activin receptor type-2B | 5.4 | 5.4 | 5.4 | pKd | 1 |
Homo sapiens | Bone morphogenetic protein receptor type-1A | 7.2 | 7.2 | 7.2 | pKd | 1 |
Homo sapiens | Bone morphogenetic protein receptor type-1B | 7.5 | 7.5 | 7.5 | pKd | 1 |
Homo sapiens | Breakpoint cluster region protein | 7.8 | 7.8 | 7.8 | pKd | 2 |
Homo sapiens | Chaperone activity of bc1 complex-like, mitochondrial | 6.6 | 6.6 | 6.6 | pKd | 1 |
Homo sapiens | Cyclin-dependent kinase 2 | 5 | 5 | 5 | pIC50 | 1 |
Homo sapiens | Discoidin domain-containing receptor 2 | 4.4 | 4.4 | 4.4 | pKd | 1 |
Homo sapiens | Ephrin type-A receptor 1 | 8 | 8 | 8 | pKd | 1 |
Homo sapiens | Ephrin type-A receptor 2 | 6.1 | 6.1 | 6.1 | pKd | 1 |
Homo sapiens | Ephrin type-A receptor 4 | 6 | 6 | 6 | pKd | 1 |
Homo sapiens | Ephrin type-A receptor 5 | 5.6 | 5.6 | 5.6 | pKd | 1 |
Homo sapiens | Ephrin type-B receptor 2 | 5 | 5 | 5 | pKd | 1 |
Homo sapiens | Ephrin type-B receptor 4 | 5.4 | 5.4 | 5.4 | pKd | 1 |
Homo sapiens | Ephrin type-B receptor 6 | 5.4 | 5.4 | 5.4 | pKd | 1 |
Homo sapiens | Epidermal growth factor receptor erbB1 | 5.6 | 5.6 | 7.2 | pIC50 | 4 |
Homo sapiens | Epithelial discoidin domain-containing receptor 1 | 5.4 | 5.4 | 5.4 | pKd | 1 |
Homo sapiens | Mitogen-activated protein kinase kinase kinase kinase 4 | 6 | 6 | 6 | pKd | 1 |
Homo sapiens | Mitogen-activated protein kinase kinase kinase kinase 5 | 4.6 | 4.6 | 4.6 | pKd | 1 |
Homo sapiens | Mixed lineage kinase 7 | 5.5 | 5.5 | 5.5 | pKd | 1 |
Homo sapiens | Platelet-derived growth factor receptor alpha | 5 | 5 | 5 | pIC50 | 1 |
Homo sapiens | Platelet-derived growth factor receptor beta | 6.2 | 6.2 | 6.2 | pKd | 1 |
Homo sapiens | Receptor-interacting serine/threonine-protein kinase 3 | 5.8 | 5.8 | 5.8 | pKd | 1 |
Homo sapiens | Serine/threonine-protein kinase 10 | 4.9 | 4.9 | 4.9 | pKd | 1 |
Homo sapiens | Serine/threonine-protein kinase 2 | 4.5 | 4.5 | 4.5 | pKd | 1 |
Homo sapiens | Serine/threonine-protein kinase GAK | 7 | 7 | 7 | pKd | 1 |
Homo sapiens | Serine/threonine-protein kinase RIPK2 | 8.7 | 8.7 | 8.7 | pKd | 1 |
Homo sapiens | Serine/threonine-protein kinase SIK2 | 5.9 | 5.9 | 5.9 | pKd | 1 |
Homo sapiens | Serine/threonine-protein kinase SIK3 | 5.3 | 5.3 | 5.3 | pKd | 1 |
Homo sapiens | Stem cell growth factor receptor | 6.7 | 6.7 | 6.7 | pIC50 | 3 |
Homo sapiens | TGF-beta receptor type I | 6.7 | 6.7 | 6.7 | pKd | 1 |
Homo sapiens | TRAF2- and NCK-interacting kinase | 5.9 | 5.9 | 5.9 | pKd | 1 |
Homo sapiens | Tyrosine- and threonine-specific cdc2-inhibitory kinase | 5 | 5 | 6.4 | pIC50 | 2 |
Homo sapiens | Tyrosine- and threonine-specific cdc2-inhibitory kinase | 5.6 | 5.6 | 5.6 | pKd | 1 |
Homo sapiens | Tyrosine- and threonine-specific cdc2-inhibitory kinase | 5.3 | 5.3 | 7.4 | pKi | 2 |
Homo sapiens | Tyrosine kinase non-receptor protein 2 | 5.3 | 5.3 | 5.3 | pKd | 1 |
Homo sapiens | Tyrosine-protein kinase ABL | 7.5 | 7.5 | 7.5 | pIC50 | 3 |
Homo sapiens | Tyrosine-protein kinase ABL | 7.3 | 7.3 | 7.3 | pKd | 1 |
Homo sapiens | Tyrosine-protein kinase ABL2 | 7 | 7 | 7 | pKd | 1 |
Homo sapiens | Tyrosine-protein kinase BRK | 6.3 | 6.3 | 6.3 | pKd | 1 |
Homo sapiens | Tyrosine-protein kinase BTK | 5 | 5 | 5 | pKd | 1 |
Homo sapiens | Tyrosine-protein kinase CSK | 6.1 | 6.1 | 6.1 | pIC50 | 3 |
Homo sapiens | Tyrosine-protein kinase CSK | 4.4 | 4.4 | 4.4 | pKd | 1 |
Homo sapiens | Tyrosine-protein kinase FGR | 6 | 6 | 6 | pKd | 1 |
Homo sapiens | Tyrosine-protein kinase FRK | 5.6 | 5.6 | 5.6 | pKd | 1 |
Homo sapiens | Tyrosine-protein kinase FYN | 7 | 7 | 7 | pKd | 1 |
Homo sapiens | Tyrosine-protein kinase HCK | 7 | 7 | 7 | pKd | 1 |
Homo sapiens | Tyrosine-protein kinase LCK | 8.4 | 8.4 | 8.4 | pIC50 | 1 |
Homo sapiens | Tyrosine-protein kinase LCK | 8.1 | 8.1 | 8.1 | pKd | 1 |
Homo sapiens | Tyrosine-protein kinase Lyn | 7 | 7 | 7 | pKd | 1 |
Homo sapiens | Tyrosine-protein kinase receptor FLT3 | 6.9 | 6.9 | 6.9 | pKd | 1 |
Homo sapiens | Tyrosine-protein kinase receptor RET | 6.8 | 6.8 | 6.8 | pKd | 1 |
Homo sapiens | Tyrosine-protein kinase SRC | 8.6 | 7.1 | 9 | pIC50 | 9 |
Homo sapiens | Tyrosine-protein kinase SRC | 6.9 | 6.9 | 6.9 | pKd | 1 |
Homo sapiens | Tyrosine-protein kinase YES | 8.4 | 8.2 | 9.2 | pIC50 | 5 |
Homo sapiens | Tyrosine-protein kinase YES | 7 | 7 | 7 | pKd | 1 |
Homo sapiens | Vascular endothelial growth factor receptor 2 | 4.7 | 4.7 | 4.7 | pIC50 | 2 |