KLIFS - the structural kinase database

Structure information


PDB:	4C8B
PubMed:	26320862
Release date:	2013-10-16
Resolution:	2.75 Å

Kinase:	RIPK2
Family:	RIPK
Group:	TKL
Species:	HUMAN

Quality Score:	5.2
Missing Residues:	2
Missing Atoms:	38

DFG conformation:	out
αC-helix conformation:	in
Salt bridge K^III.17 and E^αC.24:	Yes (2.8Å)


ASP rotation (xDFG.81) :	215°
PHE rotation (xDFG.82) :	209°
Activation loop position:	2.3Å
αC-helix position:	18.8Å

G-rich loop angle:	53.8°
G-rich loop distance:	16.3Å
G-rich loop rotation:	56°

Other models from this PDB:

2D & 3D views

Binding pocket waters

No waters were found in the defined clusters

Binding pocket sequence

Uniprot	RYLSRGASGTVSSVAVKHLDVLREAEILHKARSYILPILGIGIVTEYMPNGSLNELLHRHNMTPPLLHHDLKTQNILLIADFGLS
Structure:	RYLSRGASGTVSSVAVKHLDVLREAEILHKARSYILPILGIGIVTEYMPNGSLNELLHRHNMTPPLLHHDLKTQNILLIADFG__

Modified residues

No modified residues identified.

Orthosteric ligand

Ligand HET-code: 0LI
Ligand Name: 3-(imidazo[1,2-b]pyridazin-3-ylethynyl)-4-methyl-N-{4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl}benzamide

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 R
22

2 Y
23

3 L
24

4 S
25

5 R
26

6 G
27

7 A
28

8 S
29

9 G
30

10 T
31

11 V
32

12 S
33

13 S
34

14 V
44

15 A
45

16 V
46

17 K
47

18 H
48

19 L
49

20 D
62

■

αC

b.l

IV

21 V
63

22 L
64

23 R
65

24 E
66

25 A
67

26 E
68

27 I
69

28 L
70

29 H
71

30 K
72

31 A
73

32 R
74

33 S
76

34 Y
77

35 I
78

36 L
79

37 P
80

38 I
81

39 L
82

40 G
83

■▲

■

IV

V

GK

hinge

linker

αD

αE

41 I
84

42 G
92

43 I
93

44 V
94

45 T
95

46 E
96

47 Y
97

48 M
98

49 P
99

50 N
100

51 G
101

52 S
102

53 L
103

54 N
104

55 E
105

56 L
106

57 L
107

58 H
108

59 R
109

60 H
136

■

■♦

■▲

αE

VI

c.l

VII

VIII

x

61 N
137

62 M
138

63 T
139

64 P
140

65 P
141

66 L
142

67 L
143

68 H
144

69 H
145

70 D
146

71 L
147

72 K
148

73 T
149

74 Q
150

75 N
151

76 I
152

77 L
153

78 L
154

79 I
162

80 A
163

■

DFG

a.l

81 D
164

82 F
165

83 G
188

84 _
_

85 _
_

■▲

■♦

Interaction pattern search

Search KLIFS for kinase-ligand complexes with similar interaction patterns:

Binding affinities

ChEMBL ID:CHEMBL1171837
Bioaffinities: 119 records for 62 kinase(s)

Species	Kinase (ChEMBL naming)	Median	Min	Max	Type	Records
Homo sapiens	Breakpoint cluster region protein	7.3	7.3	7.3	pKd	2
Homo sapiens	CaM-kinase kinase beta	5.8	5.8	5.8	pKd	1
Homo sapiens	c-Jun N-terminal kinase 2	5.1	5.1	5.1	pKd	1
Homo sapiens	Discoidin domain-containing receptor 2	7.1	7.1	7.1	pKd	1
Homo sapiens	Dual specificity mitogen-activated protein kinase kinase 5	5.5	5.5	5.5	pKd	1
Homo sapiens	Ephrin type-A receptor 1	5.9	5.9	5.9	pKd	1
Homo sapiens	Ephrin type-A receptor 2	7.6	7.6	7.6	pKd	1
Homo sapiens	Ephrin type-A receptor 4	4.8	4.8	4.8	pKd	1
Homo sapiens	Ephrin type-A receptor 5	8.1	8.1	8.1	pKd	1
Homo sapiens	Ephrin type-B receptor 2	5.7	5.7	5.7	pKd	1
Homo sapiens	Ephrin type-B receptor 3	6.3	6.3	6.3	pKd	1
Homo sapiens	Ephrin type-B receptor 4	5.8	5.8	5.8	pKd	1
Homo sapiens	Epithelial discoidin domain-containing receptor 1	7.8	7.8	7.8	pKd	1
Homo sapiens	Fibroblast growth factor receptor 1	8.9	8.7	9.2	pIC50	6
Homo sapiens	Fibroblast growth factor receptor 2	8.7	8.7	8.9	pIC50	2
Homo sapiens	Fibroblast growth factor receptor 3	7.8	7.8	8	pIC50	2
Homo sapiens	Fibroblast growth factor receptor 4	8.1	8.1	8.2	pIC50	2
Homo sapiens	Interleukin-1 receptor-associated kinase 1	6.2	6.2	6.2	pKd	1
Homo sapiens	Interleukin-1 receptor-associated kinase 4	5.7	5.7	5.7	pKd	1
Homo sapiens	MAP kinase-activated protein kinase 2	6.3	6.3	6.3	pKd	1
Homo sapiens	MAP kinase p38 alpha	6.8	6.8	6.8	pKd	1
Homo sapiens	MAP kinase p38 beta	6	6	6	pKd	1
Homo sapiens	Maternal embryonic leucine zipper kinase	5.5	5.5	5.5	pKd	1
Homo sapiens	Mitogen-activated protein kinase kinase kinase 1	6.3	6.3	6.3	pKd	1
Homo sapiens	Mitogen-activated protein kinase kinase kinase kinase 1	6.1	6.1	6.1	pKd	1
Homo sapiens	Mitogen-activated protein kinase kinase kinase kinase 2	7.4	7.4	7.4	pKd	1
Homo sapiens	Mitogen-activated protein kinase kinase kinase kinase 4	6.5	6.5	6.5	pKd	1
Homo sapiens	Mixed lineage kinase 7	7.4	7.4	7.4	pKd	1
Homo sapiens	Myosin light chain kinase, smooth muscle	7	7	7	pKd	1
Homo sapiens	Non-receptor tyrosine-protein kinase TNK1	7.1	7.1	7.1	pKd	1
Homo sapiens	Platelet-derived growth factor receptor alpha	8.6	8.6	8.6	pIC50	1
Homo sapiens	Platelet-derived growth factor receptor beta	8.9	8.9	8.9	pIC50	1
Homo sapiens	Platelet-derived growth factor receptor beta	5.5	5.5	5.5	pKd	1
Homo sapiens	Protein tyrosine kinase 2 beta	6.5	6.5	6.5	pKd	1
Homo sapiens	Receptor-interacting serine/threonine-protein kinase 1	7.9	7.9	7.9	pIC50	1
Homo sapiens	Receptor-interacting serine/threonine-protein kinase 3	8.8	8.8	8.8	pIC50	1
Homo sapiens	Receptor-interacting serine/threonine-protein kinase 3	7.6	7.6	7.6	pKd	1
Homo sapiens	Serine/threonine-protein kinase B-raf	5.9	5.9	5.9	pKd	1
Homo sapiens	Serine/threonine-protein kinase GAK	5.7	5.7	5.7	pKd	1
Homo sapiens	Serine/threonine-protein kinase PCTAIRE-1	5.8	5.8	5.8	pKd	1
Homo sapiens	Serine/threonine-protein kinase PCTAIRE-2	6.5	6.5	6.5	pKd	1
Homo sapiens	Serine/threonine-protein kinase RIPK2	8.2	8.2	9	pIC50	2
Homo sapiens	Serine/threonine-protein kinase RIPK2	7.1	7.1	7.1	pKd	1
Homo sapiens	Serine/threonine-protein kinase TAO3	5.7	5.7	5.7	pKd	1
Homo sapiens	Serine/threonine-protein kinase ULK3	5.8	5.8	5.8	pKd	1
Homo sapiens	Stem cell growth factor receptor	7.8	6.9	8.8	pIC50	6
Homo sapiens	TGF-beta receptor type II	5.8	5.8	5.8	pKd	1
Homo sapiens	TRAF2- and NCK-interacting kinase	6.4	6.4	6.4	pKd	1
Homo sapiens	Tyrosine-protein kinase ABL	9	7.4	9.5	pIC50	23
Homo sapiens	Tyrosine-protein kinase ABL	7.4	7.4	7.4	pKd	1
Homo sapiens	Tyrosine-protein kinase ABL2	7.7	7.7	7.7	pKd	1
Homo sapiens	Tyrosine-protein kinase BTK	5.7	5.7	5.7	pKd	1
Homo sapiens	Tyrosine-protein kinase CSK	6.5	6.5	6.5	pKd	1
Homo sapiens	Tyrosine-protein kinase FGR	7.4	7.4	7.4	pKd	1
Homo sapiens	Tyrosine-protein kinase FRK	7	7	7	pKd	1
Homo sapiens	Tyrosine-protein kinase FYN	7.4	7.4	7.4	pKd	1
Homo sapiens	Tyrosine-protein kinase HCK	7.1	7.1	7.1	pKd	1
Homo sapiens	Tyrosine-protein kinase LCK	7.6	7.6	7.6	pKd	1
Homo sapiens	Tyrosine-protein kinase Lyn	8.7	8.7	9.6	pIC50	2
Homo sapiens	Tyrosine-protein kinase Lyn	7.6	7.6	7.6	pKd	1
Homo sapiens	Tyrosine-protein kinase receptor FLT3	9.5	9.5	9.5	pIC50	1
Homo sapiens	Tyrosine-protein kinase receptor FLT3	8.2	8.2	8.2	pKd	1
Homo sapiens	Tyrosine-protein kinase receptor RET	7.6	7.5	9.5	pIC50	4
Homo sapiens	Tyrosine-protein kinase receptor RET	7.6	7.6	7.6	pKd	1
Gallus gallus	Tyrosine-protein kinase SRC	9.1	9.1	9.1	pIC50	1
Homo sapiens	Tyrosine-protein kinase SRC	8.5	8	8.6	pIC50	3
Homo sapiens	Tyrosine-protein kinase SRC	6.4	6.4	6.4	pKd	1
Homo sapiens	Tyrosine-protein kinase YES	6.7	6.7	6.7	pKd	1
Homo sapiens	Vascular endothelial growth factor receptor 1	7.7	7.7	7.7	pIC50	1
Homo sapiens	Vascular endothelial growth factor receptor 2	8.7	7.6	8.8	pIC50	7

4C8B - chain B | Receptor interacting serine/threonine kinase 2