KLIFS - the structural kinase database

Structure information


PDB:	4QMX
PubMed:	27135311
Release date:	2015-07-01
Resolution:	1.88 Å

Kinase:	STK24 (MST3)
Family:	STE20
Group:	STE
Species:	HUMAN

Quality Score:	8
Missing Residues:	0
Missing Atoms:	0

DFG conformation:	in
αC-helix conformation:	in
Salt bridge K^III.17 and E^αC.24:	Yes (2.7Å)


ASP rotation (xDFG.81) :	349°
PHE rotation (xDFG.82) :	14°
Activation loop position:	-3.2Å
αC-helix position:	17.9Å

G-rich loop angle:	60.2°
G-rich loop distance:	17.5Å
G-rich loop rotation:	74.5°

2D & 3D views

Binding pocket waters

The following waters were found in the defined clusters:

I4

H-bond protein

I5

H-bond protein

I6

H-bond ligand

I10

H-bond protein

Binding pocket sequence

Uniprot	EKIGKGSFGEVFKVAIKIIDIQQEITVLSQCDPYVTKYYGSWIIMEYLGGGSALDLLEPYLHSEKKIHRDIKAANVLLLADFGVA
Structure:	EKIGKGSFGEVFKVAIKIIDIQQEITVLSQCDPYVTKYYGSWIIMEYLGGGSALDLLEPYLHSEKKIHRDIKAANVLLLADFGVA

Modified residues

Residue 178 (not in pocket)

Phosphorylated threonine

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 E
28

2 K
29

3 I
30

4 G
31

5 K
32

6 G
33

7 S
34

8 F
35

9 G
36

10 E
37

11 V
38

12 F
39

13 K
40

14 V
50

15 A
51

16 I
52

17 K
53

18 I
54

19 I
55

20 D
66

■

αC

b.l

IV

21 I
67

22 Q
68

23 Q
69

24 E
70

25 I
71

26 T
72

27 V
73

28 L
74

29 S
75

30 Q
76

31 C
77

32 D
78

33 P
80

34 Y
81

35 V
82

36 T
83

37 K
84

38 Y
85

39 Y
86

40 G
87

IV

V

GK

hinge

linker

αD

αE

41 S
88

42 W
96

43 I
97

44 I
98

45 M
99

46 E
100

47 Y
101

48 L
102

49 G
103

50 G
104

51 G
105

52 S
106

53 A
107

54 L
108

55 D
109

56 L
110

57 L
111

58 E
112

59 P
113

60 Y
134

■

■♦

■▲

■

αE

VI

c.l

VII

VIII

x

61 L
135

62 H
136

63 S
137

64 E
138

65 K
139

66 K
140

67 I
141

68 H
142

69 R
143

70 D
144

71 I
145

72 K
146

73 A
147

74 A
148

75 N
149

76 V
150

77 L
151

78 L
152

79 L
160

80 A
161

■

DFG

a.l

81 D
162

82 F
163

83 G
164

84 V
165

85 A
166

■

Interaction pattern search

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

Binding affinities

ChEMBL ID:CHEMBL217092
Bioaffinities: 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

4QMX - chain A | Serine/threonine kinase 24

Structure information

2D & 3D views

Binding pocket waters

Binding pocket sequence

Modified residues

Orthosteric ligand

Kinase-ligand interactions

Interaction pattern search

Binding affinities