4UXL - chain A | ROS proto-oncogene 1 , receptor tyrosine kinase
Structure information
PDB: | 4UXL |
PubMed: | 25733882 |
Release date: | 2015-03-11 |
Resolution: | 2.4 Å |
Kinase: | ROS1 (ROS) |
Family: | Sev |
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 (4.1Å) |
ASP rotation (xDFG.81) : | 3° |
PHE rotation (xDFG.82) : | 9° |
Activation loop position: | -4.2Å |
αC-helix position: | 16.6Å |
G-rich loop angle: | 58.9° |
G-rich loop distance: | 17.7Å |
G-rich loop rotation: | 68.9° |
2D & 3D views
Binding pocket waters
The following waters were found in the defined clusters:
I1
H-bond ligand
H-bond protein
I2
H-bond protein
I4
H-bond protein
I5
H-bond protein
I10
H-bond protein
Binding pocket sequence
Uniprot | LLLGSGAFGEVYEVAVKTLEFLKEAHLMSKFNPNILKQLGVYIILELMEGGDLLTYLRKYLERMHFIHRDLAARNCLVIGDFGLA |
Structure: | LLLGSGAFGEVYEVAVKTLEFLKEAHLMSKFNPNILKQLGVYIILELMEGGDLLTYLRKYLERMHFIHRDLAARNCLVIGDFGLA |
Modified residues
No modified residues identified.
Orthosteric ligand
Ligand HET-code: 5P8
Ligand Name: (10R)-7-amino-12-fluoro-2,10,16-trimethyl-15-oxo-10,15,16,17-tetrahydro-2H-8,4-(metheno)pyrazolo[4,3-h][2,5,11]benzoxadiazacyclotetradecine-3-carbonitrile
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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 L 1949 | 2 L 1950 | 3 L 1951 | 4 G 1952 | 5 S 1953 | 6 G 1954 | 7 A 1955 | 8 F 1956 | 9 G 1957 | 10 E 1958 | 11 V 1959 | 12 Y 1960 | 13 E 1961 | 14 V 1977 | 15 A 1978 | 16 V 1979 | 17 K 1980 | 18 T 1981 | 19 L 1982 | 20 E 1993 |
■ | ■ | ■ | ■ | ■ | |||||||||||||||
αC | b.l | IV | |||||||||||||||||
21 F 1994 | 22 L 1995 | 23 K 1996 | 24 E 1997 | 25 A 1998 | 26 H 1999 | 27 L 2000 | 28 M 2001 | 29 S 2002 | 30 K 2003 | 31 F 2004 | 32 N 2005 | 33 P 2007 | 34 N 2008 | 35 I 2009 | 36 L 2010 | 37 K 2011 | 38 Q 2012 | 39 L 2013 | 40 G 2014 |
IV | V | GK | hinge | linker | αD | αE | |||||||||||||
41 V 2015 | 42 Y 2023 | 43 I 2024 | 44 I 2025 | 45 L 2026 | 46 E 2027 | 47 L 2028 | 48 M 2029 | 49 E 2030 | 50 G 2031 | 51 G 2032 | 52 D 2033 | 53 L 2034 | 54 L 2035 | 55 T 2036 | 56 Y 2037 | 57 L 2038 | 58 R 2039 | 59 K 2040 | 60 Y 2069 |
■ | ▲ | ■ | ■▲ | ■ | ■ | ■ | |||||||||||||
αE | VI | c.l | VII | VIII | x | ||||||||||||||
61 L 2070 | 62 E 2071 | 63 R 2072 | 64 M 2073 | 65 H 2074 | 66 F 2075 | 67 I 2076 | 68 H 2077 | 69 R 2078 | 70 D 2079 | 71 L 2080 | 72 A 2081 | 73 A 2082 | 74 R 2083 | 75 N 2084 | 76 C 2085 | 77 L 2086 | 78 V 2087 | 79 I 2100 | 80 G 2101 |
■ | ■ | ■ | |||||||||||||||||
DFG | a.l | ||||||||||||||||||
81 D 2102 | 82 F 2103 | 83 G 2104 | 84 L 2105 | 85 A 2106 | |||||||||||||||
■ |
Binding affinities
ChEMBL ID:CHEMBL3286830Bioaffinities: 26 records for 12 kinase(s)
Species | Kinase (ChEMBL naming) | Median | Min | Max | Type | Records |
---|---|---|---|---|---|---|
Homo sapiens | ALK tyrosine kinase receptor | 8.1 | 7.1 | 9.7 | pIC50 | 9 |
Homo sapiens | ALK tyrosine kinase receptor | 9.2 | 8.1 | 9.2 | pKi | 4 |
Homo sapiens | Focal adhesion kinase 1 | 7.8 | 7.8 | 7.8 | pIC50 | 1 |
Homo sapiens | Leukocyte tyrosine kinase receptor | 8.6 | 8.6 | 8.6 | pIC50 | 1 |
Homo sapiens | Nerve growth factor receptor Trk-A | 7.6 | 7.6 | 7.6 | pIC50 | 1 |
Homo sapiens | Neurotrophic tyrosine kinase receptor type 2 | 7.6 | 7.6 | 7.6 | pKi | 2 |
Homo sapiens | NT-3 growth factor receptor | 7.3 | 7.3 | 7.3 | pIC50 | 1 |
Homo sapiens | Protein tyrosine kinase 2 beta | 7.9 | 7.9 | 7.9 | pIC50 | 1 |
Homo sapiens | Proto-oncogene tyrosine-protein kinase ROS | 7.9 | 7.9 | 10 | pKi | 2 |
Homo sapiens | Tyrosine kinase non-receptor protein 2 | 7.8 | 7.8 | 7.8 | pIC50 | 1 |
Homo sapiens | Tyrosine-protein kinase FER | 8.5 | 8.5 | 8.5 | pIC50 | 1 |
Homo sapiens | Tyrosine-protein kinase FES | 8.2 | 8.2 | 8.2 | pIC50 | 1 |
Homo sapiens | Tyrosine-protein kinase FRK | 7.3 | 7.3 | 7.3 | pIC50 | 1 |