3ZBF - chain A | ROS proto-oncogene 1 , receptor tyrosine kinase
Structure information
PDB:3ZBF
PubMed:23724914
Release date:2013-06-12
Resolution:2.2 Å
 
Kinase:ROS1 (ROS)
Family:Sev
Group:TK
Species:HUMAN
 
Quality Score:6.8
Missing Residues:3
Missing Atoms:0
DFG conformation:in
αC-helix conformation:in
Salt bridge KIII.17 and EαC.24:Yes (3.5Å)
 
 
ASP rotation (xDFG.81) :
PHE rotation (xDFG.82) :14°
Activation loop position:-4.2Å
αC-helix position:17Å
 
G-rich loop angle:-
G-rich loop distance:-
G-rich loop rotation:-
2D & 3D views

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


Modified residues
No modified residues identified.
Orthosteric ligand
2D structure of the orthosteric ligand
Ligand HET-code: VGH
Ligand Name: 3-[(1R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy]-5-(1-piperidin-4-yl-1H-pyrazol-4-yl)pyridin-2-amine

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  • LABELS
  • KLIFS residue #
  • Amino Acid
  • None
  • COLORS
  • Interaction types
  • KLIFS (all res.)
  • KLIFS (interacting res.)
  • None
  • OTHER
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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 L
1949
2 L
1950
3 L
1951
4 G
1952
5 S
1953
6 G
1957
7 _
_
8 _
_
9 _
_
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:
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Binding affinities
ChEMBL ID:CHEMBL601719
Bioaffinities: 368 records for 154 kinase(s)

Species Kinase (ChEMBL naming) Median Min Max Type Records
Homo sapiensActivin receptor type-16.46.46.4pKd1
Homo sapiensActivin receptor type-1B6.16.16.1pKd1
Homo sapiensAdaptor-associated kinase5.65.65.6pKd1
Homo sapiensALK tyrosine kinase receptor5.74.69.3pEC504
Homo sapiensALK tyrosine kinase receptor6.94.59.2pIC5068
Homo sapiensALK tyrosine kinase receptor8.58.48.5pKd3
Homo sapiensALK tyrosine kinase receptor8.18.19.1pKi5
Mus musculusALK tyrosine kinase receptor7.17.17.1pIC501
Homo sapiensAMP-activated protein kinase, alpha-1 subunit5.65.65.6pKd1
Homo sapiensAnkyrin repeat and protein kinase domain-containing protein 16.16.16.1pKd1
Homo sapiensBMP-2-inducible protein kinase6.16.16.1pKd1
Homo sapiensBone morphogenetic protein receptor type-1B6.66.66.6pKd1
Homo sapiensBreakpoint cluster region protein5.65.65.6pKd2
Homo sapiensCaM-kinase kinase beta5.85.85.8pKd1
Homo sapiensCyclin-dependent kinase 76.56.56.5pKd1
Homo sapiensCyclin-dependent kinase-like 25.75.75.7pKd1
Homo sapiensDual serine/threonine and tyrosine protein kinase6.46.46.4pKd1
Homo sapiensDual specificity mitogen-activated protein kinase kinase 35.55.55.5pKd1
Homo sapiensDual specificity testis-specific protein kinase 16.46.46.4pKd1
Homo sapiensDual-specificity tyrosine-phosphorylation regulated kinase 25.45.45.4pKd1
Homo sapiensEphrin type-A receptor 16.96.96.9pKd1
Homo sapiensEphrin type-A receptor 25.95.97pKd2
Homo sapiensEphrin type-A receptor 36.26.26.2pKd1
Homo sapiensEphrin type-A receptor 46.46.46.4pKd1
Homo sapiensEphrin type-A receptor 5666pKd1
Homo sapiensEphrin type-A receptor 67.27.27.2pKd1
Homo sapiensEphrin type-A receptor 76.36.36.3pKd1
Homo sapiensEphrin type-A receptor 86.66.66.6pKd1
Homo sapiensEphrin type-B receptor 16.96.96.9pKd1
Homo sapiensEphrin type-B receptor 46.26.26.2pKd1
Homo sapiensEphrin type-B receptor 66.36.38.2pKd2
Homo sapiensEpidermal growth factor receptor erbB16.26.26.2pIC501
Homo sapiensEpidermal growth factor receptor erbB15.65.65.6pKd2
Homo sapiensEpithelial discoidin domain-containing receptor 16.36.36.3pKd1
Homo sapiensFibroblast growth factor receptor 35.55.55.6pKd2
Homo sapiensFocal adhesion kinase 16.26.26.5pKd2
Homo sapiensG protein-coupled receptor kinase 45.45.45.4pKd1
Homo sapiensHepatocyte growth factor receptor8.57.79.3pIC5027
Homo sapiensHepatocyte growth factor receptor8.78.19.7pKd6
Homo sapiensHepatocyte growth factor receptor8.78.48.7pKi3
Homo sapiensHomeodomain-interacting protein kinase 45.45.45.4pKd1
Homo sapiensInhibitor of nuclear factor kappa B kinase beta subunit5.35.35.3pKd1
Homo sapiensInhibitor of nuclear factor kappa B kinase epsilon subunit5.65.66.2pKd2
Homo sapiensInsulin-like growth factor I receptor6.86.86.8pIC501
Homo sapiensInsulin-like growth factor I receptor6.16.16.1pKd1
Homo sapiensInsulin receptor6.25.57pIC505
Homo sapiensInsulin receptor6.56.56.5pKd1
Homo sapiensInsulin receptor-related protein6.26.26.2pKd1
Homo sapiensInterferon-induced, double-stranded RNA-activated protein kinase666pKd1
Homo sapiensInterleukin-1 receptor-associated kinase 15.45.47.3pKd2
Homo sapiensInterleukin-1 receptor-associated kinase 36.26.27.5pKd2
Homo sapiensInterleukin-1 receptor-associated kinase 45.45.45.4pKd1
Homo sapiensLeukocyte tyrosine kinase receptor7.97.97.9pKd1
Homo sapiensLIM domain kinase 15.75.76.1pKd2
Homo sapiensLIM domain kinase 25.45.46.2pKd2
Homo sapiensMacrophage colony stimulating factor receptor6.76.76.7pKd1
Homo sapiensMacrophage-stimulating protein receptor6.56.56.7pIC502
Homo sapiensMacrophage-stimulating protein receptor7.17.17.6pKd2
Mus musculusMacrophage-stimulating protein receptor7.17.17.1pIC501
Homo sapiensMisshapen-like kinase 15.45.45.4pKd1
Homo sapiensMitogen-activated protein kinase 76.36.36.3pKd1
Homo sapiensMitogen-activated protein kinase kinase kinase 15.75.76pKd2
Homo sapiensMitogen-activated protein kinase kinase kinase 126.86.86.8pKd1
Homo sapiensMitogen-activated protein kinase kinase kinase 136.66.66.6pKd1
Homo sapiensMitogen-activated protein kinase kinase kinase 155.65.65.6pKd1
Homo sapiensMitogen-activated protein kinase kinase kinase 27.17.17.1pKd1
Homo sapiensMitogen-activated protein kinase kinase kinase 3777pKd1
Homo sapiensMitogen-activated protein kinase kinase kinase 75.85.85.8pKd1
Homo sapiensMitogen-activated protein kinase kinase kinase kinase 15.75.77.4pKd2
Homo sapiensMitogen-activated protein kinase kinase kinase kinase 26.76.77.1pKd2
Homo sapiensMitogen-activated protein kinase kinase kinase kinase 35.65.67.1pKd2
Homo sapiensMitogen-activated protein kinase kinase kinase kinase 5667.1pKd2
Homo sapiensMixed lineage kinase domain-like protein6.76.76.7pKd1
Homo sapiensMuscle, skeletal receptor tyrosine protein kinase6.66.66.6pKd1
Homo sapiensMyotonin-protein kinase5.95.95.9pKd1
Homo sapiensNerve growth factor receptor Trk-A6.26.26.2pIC501
Homo sapiensNerve growth factor receptor Trk-A777pKd1
Homo sapiensNeurotrophic tyrosine kinase receptor type 26.46.48.7pIC502
Homo sapiensNeurotrophic tyrosine kinase receptor type 27.47.47.4pKd1
Homo sapiensNon-receptor tyrosine-protein kinase TNK16.56.56.5pKd1
Homo sapiensNT-3 growth factor receptor7.17.17.1pKd1
Homo sapiensNUAK family SNF1-like kinase 26.96.96.9pKd1
Homo sapiensPeripheral plasma membrane protein CASK6.96.96.9pKd1
Homo sapiensPhosphatidylinositol-4-phosphate 5-kinase type-1 alpha5.55.55.5pKd1
Homo sapiensPITSLRE serine/threonine-protein kinase CDC2L16.16.16.1pKd1
Homo sapiensPITSLRE serine/threonine-protein kinase CDC2L26.46.46.4pKd1
Homo sapiensProtein kinase C mu666pKd1
Homo sapiensProtein kinase C nu6.16.16.3pKd2
Homo sapiensProtein tyrosine kinase 2 beta6.76.76.7pKd1
Homo sapiensProto-oncogene tyrosine-protein kinase MER8.48.48.4pKd1
Homo sapiensProto-oncogene tyrosine-protein kinase ROS85.29.2pIC5010
Homo sapiensProto-oncogene tyrosine-protein kinase ROS8.48.48.4pKd1
Homo sapiensProto-oncogene tyrosine-protein kinase ROS8.26.59.2pKi3
Homo sapiensPutative uncharacterized serine/threonine-protein kinase SgK1106.66.66.6pKd1
Homo sapiensReceptor-interacting serine/threonine-protein kinase 15.85.85.9pKd2
Homo sapiensReceptor-interacting serine/threonine-protein kinase 35.25.25.2pKd1
Homo sapiensReceptor-interacting serine/threonine-protein kinase 45.75.75.7pKd1
Homo sapiensRho-associated protein kinase 15.45.45.4pKd1
Homo sapiensRho-associated protein kinase 25.55.55.5pKd1
Homo sapiensRibosomal protein S6 kinase 16.26.26.2pKd1
Homo sapiensSerine/threonine-protein kinase 105.65.67.4pKd2
Homo sapiensSerine/threonine-protein kinase 25.95.97.8pKd2
Homo sapiensSerine/threonine-protein kinase 356.26.26.2pKd1
Homo sapiensSerine/threonine-protein kinase Aurora-A6.66.37.1pKd3
Homo sapiensSerine/threonine-protein kinase Aurora-B5.95.97.1pKd2
Homo sapiensSerine/threonine-protein kinase Aurora-C5.45.45.4pKd1
Homo sapiensSerine/threonine-protein kinase D25.25.25.2pKd1
Homo sapiensSerine/threonine-protein kinase DCLK16.56.56.5pKd1
Homo sapiensSerine/threonine-protein kinase DCLK26.46.46.4pKd1
Homo sapiensSerine/threonine-protein kinase MST16.26.26.2pKd1
Homo sapiensSerine/threonine-protein kinase MST2666pKd1
Homo sapiensSerine/threonine-protein kinase MST45.65.65.6pKd1
Homo sapiensSerine/threonine-protein kinase NEK75.25.25.2pKd1
Homo sapiensSerine/threonine-protein kinase NEK96.16.16.1pKd1
Homo sapiensSerine/threonine-protein kinase NIM15.35.35.3pKd1
Homo sapiensSerine/threonine-protein kinase PLK47.27.27.2pKd1
Homo sapiensSerine/threonine-protein kinase RIO15.25.25.2pKd1
Homo sapiensSerine/threonine-protein kinase RIO35.45.45.4pKd1
Homo sapiensSerine/threonine-protein kinase RIPK26.16.16.1pKd1
Homo sapiensSerine/threonine-protein kinase SBK15.95.95.9pKd1
Homo sapiensSerine/threonine-protein kinase SIK26.76.76.7pKd1
Homo sapiensSerine/threonine-protein kinase SRPK15.85.85.8pKd1
Homo sapiensSerine/threonine-protein kinase SRPK35.15.15.1pKd1
Homo sapiensSerine/threonine-protein kinase TAO15.95.95.9pKd1
Homo sapiensSerine/threonine-protein kinase TAO26.16.16.1pKd1
Homo sapiensSerine/threonine-protein kinase TAO36.36.36.3pKd1
Homo sapiensSerine/threonine-protein kinase TBK16.26.26.2pKd1
Homo sapiensSerine/threonine-protein kinase TNNI3K777pKd1
Homo sapiensSerine/threonine-protein kinase ULK1666pKd1
Homo sapiensSerine/threonine-protein kinase ULK25.85.85.8pKd1
Homo sapiensSerine/threonine-protein kinase ULK35.25.25.2pKd1
Homo sapiensSPS1/STE20-related protein kinase YSK4666pKd1
Homo sapiensStem cell growth factor receptor5.45.46.1pKd2
Homo sapiensTGF-beta receptor type I5.55.56pKd2
Homo sapiensTyrosine kinase non-receptor protein 26.16.16.1pKd1
Homo sapiensTyrosine-protein kinase ABL5.95.97.6pIC502
Homo sapiensTyrosine-protein kinase ABL75.58pKd16
Mus musculusTyrosine-protein kinase ABL5.95.95.9pIC501
Homo sapiensTyrosine-protein kinase ABL26.36.36.4pKd2
Homo sapiensTyrosine-protein kinase BLK777pKd1
Homo sapiensTyrosine-protein kinase BMX5.45.45.4pKd1
Homo sapiensTyrosine-protein kinase BTK5.15.15.1pKd1
Homo sapiensTyrosine-protein kinase FER6.66.66.6pKd1
Homo sapiensTyrosine-protein kinase FES6.46.46.4pKd1
Homo sapiensTyrosine-protein kinase FGR6.26.26.2pKd1
Homo sapiensTyrosine-protein kinase FRK5.55.55.5pKd1
Homo sapiensTyrosine-protein kinase FYN5.95.95.9pKd1
Homo sapiensTyrosine-protein kinase ITK/TSK5.75.75.7pKd1
Homo sapiensTyrosine-protein kinase JAK16.36.36.3pIC502
Homo sapiensTyrosine-protein kinase JAK16.56.56.5pKd2
Homo sapiensTyrosine-protein kinase JAK27.67.67.6pIC502
Homo sapiensTyrosine-protein kinase JAK26.56.58pKd4
Homo sapiensTyrosine-protein kinase JAK35.95.95.9pIC502
Homo sapiensTyrosine-protein kinase JAK36.76.76.7pKd2
Homo sapiensTyrosine-protein kinase LCK5.65.65.6pIC502
Homo sapiensTyrosine-protein kinase LCK5.95.97.5pKd2
Homo sapiensTyrosine-protein kinase Lyn666pKd1
Homo sapiensTyrosine-protein kinase receptor FLT36.15.56.7pKd7
Homo sapiensTyrosine-protein kinase receptor RET5.75.75.9pKd2
Homo sapiensTyrosine-protein kinase receptor Tie-1777pKd1
Homo sapiensTyrosine-protein kinase receptor TYRO36.16.16.1pKd1
Homo sapiensTyrosine-protein kinase receptor UFO6.56.56.5pIC503
Homo sapiensTyrosine-protein kinase receptor UFO8.18.18.1pKd1
Homo sapiensTyrosine-protein kinase SRC6.36.36.3pKd1
Homo sapiensTyrosine-protein kinase SYK5.65.65.6pKd1
Homo sapiensTyrosine-protein kinase TIE-26.46.48.3pIC502
Homo sapiensTyrosine-protein kinase TIE-26.66.66.6pKd1
Mus musculusTyrosine-protein kinase TIE-26.46.46.4pIC501
Homo sapiensTyrosine-protein kinase TXK6.16.16.1pKd1
Homo sapiensTyrosine-protein kinase TYK25.95.95.9pIC502
Homo sapiensTyrosine-protein kinase TYK25.75.76.7pKd4
Homo sapiensTyrosine-protein kinase YES6.16.16.1pKd1
Homo sapiensTyrosine-protein kinase ZAP-705.45.45.4pKd1
Homo sapiensUncharacterized aarF domain-containing protein kinase 4666pKd1
Homo sapiensVascular endothelial growth factor receptor 15.65.65.6pKd1