KLIFS - the structural kinase database

Structure information


PDB:	5HES
PubMed:	26999302
Release date:	2016-03-30
Resolution:	2.14 Å

Kinase:	MAP3K20 (ZAK)
Family:	MLK
Group:	TKL
Species:	HUMAN

Quality Score:	9
Missing Residues:	2
Missing Atoms:	2

DFG conformation:	in
αC-helix conformation:	out
Salt bridge K^III.17 and E^αC.24:	No (12.3Å)


ASP rotation (xDFG.81) :	333°
PHE rotation (xDFG.82) :	327°
Activation loop position:	-4.4Å
αC-helix position:	21.3Å

G-rich loop angle:	59.2°
G-rich loop distance:	17.3Å
G-rich loop rotation:	15.3°

Other models from this PDB:

2D & 3D views

Binding pocket waters

The following waters were found in the defined clusters:

I3

H-bond protein

I10

H-bond ligand

Binding pocket sequence

Uniprot	ENCGGGSFGSVYRVAVKKLKIEKEAEILSVLSRNIIQFYGVGIVTEYASLGSLYDYINSMEAPVKVIHRDLKSRNVVIICDFGAS
Structure:	ENCGGGSFGSVYRVAVKKLKIEKEAEILSVLSRNIIQFYGVGIVTEYASLGSLYDYINSMEAPVKVIHRDLKSRNVVIICDFG__

Modified residues

No modified residues identified.

Orthosteric ligand

Ligand HET-code: 032
Ligand Name: N-(3-{[5-(4-chlorophenyl)-1H-pyrrolo[2,3-b]pyridin-3-yl]carbonyl}-2,4-difluorophenyl)propane-1-sulfonamide

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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 E
20

2 N
21

3 C
22

4 G
23

5 G
24

6 G
25

7 S
26

8 F
27

9 G
28

10 S
29

11 V
30

12 Y
31

13 R
32

14 V
42

15 A
43

16 V
44

17 K
45

18 K
46

19 L
47

20 K
49

■

■♦

■

αC

b.l

IV

21 I
50

22 E
51

23 K
52

24 E
53

25 A
54

26 E
55

27 I
56

28 L
57

29 S
58

30 V
59

31 L
60

32 S
61

33 R
63

34 N
64

35 I
65

36 I
66

37 Q
67

38 F
68

39 Y
69

40 G
70

■

IV

V

GK

hinge

linker

αD

αE

41 V
71

42 G
79

43 I
80

44 V
81

45 T
82

46 E
83

47 Y
84

48 A
85

49 S
86

50 L
87

51 G
88

52 S
89

53 L
90

54 Y
91

55 D
92

56 Y
93

57 I
94

58 N
95

59 S
96

60 M
123

■

▲

■♦♦

■▲

■

αE

VI

c.l

VII

VIII

x

61 E
124

62 A
125

63 P
126

64 V
127

65 K
128

66 V
129

67 I
130

68 H
131

69 R
132

70 D
133

71 L
134

72 K
135

73 S
136

74 R
137

75 N
138

76 V
139

77 V
140

78 I
141

79 I
149

80 C
150

■

DFG

a.l

81 D
151

82 F
152

83 G
153

84 _
_

85 _
_

■▲

■

■▲

Interaction pattern search

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

Binding affinities

ChEMBL ID:CHEMBL1229517
Bioaffinities: 72 records for 12 kinase(s)

Species	Kinase (ChEMBL naming)	Median	Min	Max	Type	Records
Homo sapiens	Dual specificity mitogen-activated protein kinase kinase 5	6.1	6.1	6.1	pKd	1
Homo sapiens	Mitogen-activated protein kinase kinase kinase kinase 5	5.8	5.8	5.8	pKd	1
Homo sapiens	Mixed lineage kinase 7	7.5	7.5	7.6	pIC50	2
Homo sapiens	Mixed lineage kinase 7	6.5	6.5	6.5	pKd	1
Homo sapiens	Receptor-interacting serine/threonine-protein kinase 3	5.7	5.7	5.7	pKd	1
Homo sapiens	Serine/threonine-protein kinase A-Raf	6	6	8.7	pIC50	4
Homo sapiens	Serine/threonine-protein kinase A-Raf	5.7	5.7	5.7	pKd	1
Homo sapiens	Serine/threonine-protein kinase B-raf	5.6	5.6	6.1	pEC50	2
Homo sapiens	Serine/threonine-protein kinase B-raf	7.5	5.9	8.5	pIC50	46
Homo sapiens	Serine/threonine-protein kinase B-raf	7.2	5.5	7.3	pKd	3
Mus musculus	Serine/threonine-protein kinase B-raf	7.5	7.5	7.5	pIC50	1
Homo sapiens	Serine/threonine-protein kinase RAF	6.9	6.4	7.3	pIC50	5
Homo sapiens	Serine/threonine-protein kinase RIPK2	6.4	6.4	6.4	pKd	1
Homo sapiens	TGF-beta receptor type II	5.5	5.5	5.5	pKd	1
Homo sapiens	Tyrosine-protein kinase BRK	5.9	5.9	5.9	pKd	1
Homo sapiens	Vascular endothelial growth factor receptor 2	6.4	6.4	6.4	pIC50	1

5HES - chain B (model A) | Mitogen-activated protein kinase kinase kinase MLT