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) :
PHE rotation (xDFG.82) :
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

The orthosteric binding pocket
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
UniprotLLLGSGAFGEVYEVAVKTLEFLKEAHLMSKFNPNILKQLGVYIILELMEGGDLLTYLRKYLERMHFIHRDLAARNCLVIGDFGLA
Structure:LLLGSGAFGEVYEVAVKTLEFLKEAHLMSKFNPNILKQLGVYIILELMEGGDLLTYLRKYLERMHFIHRDLAARNCLVIGDFGLA


Modified residues
No modified residues identified.
Orthosteric ligand
2D structure of the 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

  • Download image
  • 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

Interaction pattern search
Search KLIFS for kinase-ligand complexes with similar interaction patterns:
Specify the minimum similarity (0.00 no similarity, 1.00 identical)
Binding affinities
ChEMBL ID:CHEMBL3286830
Bioaffinities: 26 records for 12 kinase(s)

Species Kinase (ChEMBL naming) Median Min Max Type Records
Homo sapiensALK tyrosine kinase receptor8.17.19.7pIC509
Homo sapiensALK tyrosine kinase receptor9.28.19.2pKi4
Homo sapiensFocal adhesion kinase 17.87.87.8pIC501
Homo sapiensLeukocyte tyrosine kinase receptor8.68.68.6pIC501
Homo sapiensNerve growth factor receptor Trk-A7.67.67.6pIC501
Homo sapiensNeurotrophic tyrosine kinase receptor type 27.67.67.6pKi2
Homo sapiensNT-3 growth factor receptor7.37.37.3pIC501
Homo sapiensProtein tyrosine kinase 2 beta7.97.97.9pIC501
Homo sapiensProto-oncogene tyrosine-protein kinase ROS7.97.910pKi2
Homo sapiensTyrosine kinase non-receptor protein 27.87.87.8pIC501
Homo sapiensTyrosine-protein kinase FER8.58.58.5pIC501
Homo sapiensTyrosine-protein kinase FES8.28.28.2pIC501
Homo sapiensTyrosine-protein kinase FRK7.37.37.3pIC501