KLIFS - the structural kinase database

Structure information


PDB:	3LXN
PubMed:	20478313
Release date:	2010-06-02
Resolution:	2.5 Å

Kinase:	TYK2
Family:	JakA
Group:	TK
Species:	HUMAN

Quality Score:	8.2
Missing Residues:	0
Missing Atoms:	18

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


ASP rotation (xDFG.81) :	16°
PHE rotation (xDFG.82) :	17°
Activation loop position:	-4.9Å
αC-helix position:	18.6Å

G-rich loop angle:	47.3°
G-rich loop distance:	14.5Å
G-rich loop rotation:	63.3°

2D & 3D views

Binding pocket waters

The following waters were found in the defined clusters:

I1

H-bond protein

I4

H-bond protein

I5

H-bond protein

I7

H-bond ligand

Binding pocket sequence

Uniprot	RDLGEGHFGKVSLVAVKALGWKQEIDILRTLYEHIIKYKGCQLVMEYVPLGSLRDYLPRYLHAQHYIHRDLAARNVLLIGDFGLA
Structure:	RDLGEGHFGKVSLVAVKALGWKQEIDILRTLYEHIIKYKGCQLVMEYVPLGSLRDYLPRYLHAQHYIHRDLAARNVLLIGDFGLA

Modified residues

Residue 1054 (not in pocket)

Phosphorylated tyrosine

Orthosteric ligand

Ligand HET-code: MI1
Ligand Name: 3-{(3R,4R)-4-methyl-3-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]piperidin-1-yl}-3-oxopropanenitrile

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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 R
901

2 D
902

3 L
903

4 G
904

5 E
905

6 G
906

7 H
907

8 F
908

9 G
909

10 K
910

11 V
911

12 S
912

13 L
913

14 V
927

15 A
928

16 V
929

17 K
930

18 A
931

19 L
932

20 G
943

■

αC

b.l

IV

21 W
944

22 K
945

23 Q
946

24 E
947

25 I
948

26 D
949

27 I
950

28 L
951

29 R
952

30 T
953

31 L
954

32 Y
955

33 E
957

34 H
958

35 I
959

36 I
960

37 K
961

38 Y
962

39 K
963

40 G
964

■

IV

V

GK

hinge

linker

αD

αE

41 C
965

42 Q
975

43 L
976

44 V
977

45 M
978

46 E
979

47 Y
980

48 V
981

49 P
982

50 L
983

51 G
984

52 S
985

53 L
986

54 R
987

55 D
988

56 Y
989

57 L
990

58 P
991

59 R
992

60 Y
1013

■

▲

■♦

■▲

■

αE

VI

c.l

VII

VIII

x

61 L
1014

62 H
1015

63 A
1016

64 Q
1017

65 H
1018

66 Y
1019

67 I
1020

68 H
1021

69 R
1022

70 D
1023

71 L
1024

72 A
1025

73 A
1026

74 R
1027

75 N
1028

76 V
1029

77 L
1030

78 L
1031

79 I
1039

80 G
1040

■

DFG

a.l

81 D
1041

82 F
1042

83 G
1043

84 L
1044

85 A
1045

■

Interaction pattern search

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

Binding affinities

ChEMBL ID:CHEMBL221959
Bioaffinities: 486 records for 42 kinase(s)

Species	Kinase (ChEMBL naming)	Median	Min	Max	Type	Records
Homo sapiens	BMP-2-inducible protein kinase	5.2	5.2	5.2	pKd	1
Homo sapiens	CaM kinase I alpha	5.3	5.3	5.9	pKd	3
Homo sapiens	CaM kinase I delta	5.8	5.8	5.8	pKd	1
Homo sapiens	CaM kinase II alpha	5.5	5.5	5.5	pKd	1
Homo sapiens	CaM kinase II delta	5.6	5.6	5.6	pKd	1
Homo sapiens	Dual specificity mitogen-activated protein kinase kinase 1	6.4	6.4	6.4	pKd	1
Homo sapiens	G protein-coupled receptor kinase 7	5.4	5.4	5.4	pKd	1
Homo sapiens	Leucine-rich repeat serine/threonine-protein kinase 2	5.9	5.9	6.3	pKd	2
Homo sapiens	MAP kinase signal-integrating kinase 2	5.8	5.8	5.8	pKd	1
Homo sapiens	MAP/microtubule affinity-regulating kinase 2	5.2	5.2	5.2	pKd	1
Homo sapiens	Mitogen-activated protein kinase kinase kinase kinase 2	5.3	5.3	5.3	pKd	1
Homo sapiens	Myotonin-protein kinase	5.9	5.9	5.9	pKd	1
Homo sapiens	Non-receptor tyrosine-protein kinase TNK1	6.2	5.8	6.9	pKd	4
Homo sapiens	NUAK family SNF1-like kinase 2	6.4	6.4	6.6	pKd	3
Homo sapiens	Protein kinase C alpha	4.6	4.6	4.6	pKd	1
Homo sapiens	Protein kinase C delta	5	5	5.7	pKd	2
Homo sapiens	Protein kinase N1	6.7	6.7	7.2	pKd	4
Homo sapiens	Protein kinase N2	5.9	5.9	5.9	pKd	1
Homo sapiens	Rho-associated protein kinase 1	5.6	5.6	6.3	pKd	2
Homo sapiens	Rho-associated protein kinase 2	5.5	5.5	5.5	pIC50	2
Homo sapiens	Rho-associated protein kinase 2	5.5	5.5	6.4	pKd	2
Homo sapiens	Ribosomal protein S6 kinase alpha 1	5.9	5.9	5.9	pKd	2
Homo sapiens	Ribosomal protein S6 kinase alpha 2	5.9	5.9	6.2	pKd	6
Homo sapiens	Ribosomal protein S6 kinase alpha 6	5.9	5.9	6.3	pKd	6
Homo sapiens	Serine/threonine-protein kinase Aurora-B	6.3	6.3	6.3	pKd	1
Homo sapiens	Serine/threonine-protein kinase c-TAK1	5	5	5	pKd	1
Homo sapiens	Serine/threonine-protein kinase DCLK1	5.2	5.2	5.2	pKd	1
Homo sapiens	Serine/threonine-protein kinase DCLK3	8.4	7.9	8.4	pKd	3
Homo sapiens	Serine/threonine-protein kinase MST2	5.4	5.4	5.4	pKd	2
Mycobacterium tuberculosis	Serine/threonine-protein kinase pknB	5.7	5.7	5.7	pKd	1
Homo sapiens	Serine/threonine-protein kinase ULK3	5.2	5.2	5.2	pKd	1
Homo sapiens	Tyrosine kinase non-receptor protein 2	6	6	6	pKd	1
Homo sapiens	Tyrosine-protein kinase ABL	5.4	5.2	5.7	pKd	3
Homo sapiens	Tyrosine-protein kinase FYN	6	6	6	pKd	1
Homo sapiens	Tyrosine-protein kinase JAK1	7.3	7.3	7.4	pEC50	10
Homo sapiens	Tyrosine-protein kinase JAK1	8.5	6.9	9.3	pIC50	78
Homo sapiens	Tyrosine-protein kinase JAK1	8.8	8.8	8.8	pKd	4
Homo sapiens	Tyrosine-protein kinase JAK1	9.2	9.2	9.2	pKi	8
Homo sapiens	Tyrosine-protein kinase JAK2	7	6.7	7	pEC50	8
Homo sapiens	Tyrosine-protein kinase JAK2	7.8	5.3	9.3	pIC50	120
Homo sapiens	Tyrosine-protein kinase JAK2	8.3	8.3	9.2	pKd	8
Homo sapiens	Tyrosine-protein kinase JAK2	9.2	9	9.2	pKi	8
Mus musculus	Tyrosine-protein kinase JAK2	5.7	5.7	5.7	pIC50	1
Rattus norvegicus	Tyrosine-protein kinase JAK2	5.3	5.3	5.7	pIC50	4
Homo sapiens	Tyrosine-protein kinase JAK3	8.7	5.9	9.6	pIC50	86
Homo sapiens	Tyrosine-protein kinase JAK3	8.7	8.7	9.8	pKd	8
Homo sapiens	Tyrosine-protein kinase JAK3	9.4	9	9.6	pKi	10
Mus musculus	Tyrosine-protein kinase JAK3	6.8	6.8	7.3	pIC50	4
Homo sapiens	Tyrosine-protein kinase LCK	5.4	5.4	6.5	pIC50	3
Homo sapiens	Tyrosine-protein kinase LCK	5.8	5.8	6.3	pKd	2
Homo sapiens	Tyrosine-protein kinase receptor RET	5.5	5.5	5.5	pKd	1
Homo sapiens	Tyrosine-protein kinase TYK2	6.2	6.2	6.2	pEC50	4
Homo sapiens	Tyrosine-protein kinase TYK2	7.5	5.9	8.4	pIC50	38
Homo sapiens	Tyrosine-protein kinase TYK2	6.2	6.2	8.3	pKd	8
Homo sapiens	Tyrosine-protein kinase TYK2	8.1	8.1	8.4	pKi	8

3LXN - chain A | Tyrosine kinase 2

Structure information

2D & 3D views

Binding pocket waters

Binding pocket sequence

Modified residues

Orthosteric ligand

Kinase-ligand interactions

Interaction pattern search

Binding affinities