KLIFS - the structural kinase database

Structure information


PDB:	3EYG
PubMed:	19361440
Release date:	2009-02-03
Resolution:	1.9 Å

Kinase:	JAK1
Family:	JakA
Group:	TK
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 (2.9Å)


ASP rotation (xDFG.81) :	12°
PHE rotation (xDFG.82) :	15°
Activation loop position:	-4.8Å
αC-helix position:	18Å

G-rich loop angle:	47.4°
G-rich loop distance:	14.6Å
G-rich loop rotation:	59.7°

Other models from this PDB:

2D & 3D views

Binding pocket waters

The following waters were found in the defined clusters:

I1

H-bond protein

I2

H-bond protein

I4

No H-bonds

I5

H-bond protein

I7

H-bond ligand

I11

H-bond protein

Binding pocket sequence

Uniprot	RDLGEGHFGKVELVAVKSLDLKKEIEILRNLYENIVKYKGIKLIMEFLPSGSLKEYLPKYLGSRQYVHRDLAARNVLVIGDFGLT
Structure:	RDLGEGHFGKVELVAVKSLDLKKEIEILRNLYENIVKYKGIKLIMEFLPSGSLKEYLPKYLGSRQYVHRDLAARNVLVIGDFGLT

Modified residues

Residue 1034 (not in pocket)

Phosphorylated tyrosine

Residue 1035 (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
879

2 D
880

3 L
881

4 G
882

5 E
883

6 G
884

7 H
885

8 F
886

9 G
887

10 K
888

11 V
889

12 E
890

13 L
891

14 V
905

15 A
906

16 V
907

17 K
908

18 S
909

19 L
910

20 D
921

■

αC

b.l

IV

21 L
922

22 K
923

23 K
924

24 E
925

25 I
926

26 E
927

27 I
928

28 L
929

29 R
930

30 N
931

31 L
932

32 Y
933

33 E
935

34 N
936

35 I
937

36 V
938

37 K
939

38 Y
940

39 K
941

40 G
942

■

IV

V

GK

hinge

linker

αD

αE

41 I
943

42 K
953

43 L
954

44 I
955

45 M
956

46 E
957

47 F
958

48 L
959

49 P
960

50 S
961

51 G
962

52 S
963

53 L
964

54 K
965

55 E
966

56 Y
967

57 L
968

58 P
969

59 K
970

60 Y
993

■

▲

■♦

■▲

■

αE

VI

c.l

VII

VIII

x

61 L
994

62 G
995

63 S
996

64 R
997

65 Q
998

66 Y
999

67 V
1000

68 H
1001

69 R
1002

70 D
1003

71 L
1004

72 A
1005

73 A
1006

74 R
1007

75 N
1008

76 V
1009

77 L
1010

78 V
1011

79 I
1019

80 G
1020

■

DFG

a.l

81 D
1021

82 F
1022

83 G
1023

84 L
1024

85 T
1025

■

Interaction pattern search

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

Binding affinities

ChEMBL ID:CHEMBL221959
Bioaffinities: 553 records for 40 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
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	94
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	12
Homo sapiens	Tyrosine-protein kinase JAK2	7	6.7	7	pEC50	8
Homo sapiens	Tyrosine-protein kinase JAK2	8	5.3	9.3	pIC50	136
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	10
Mus musculus	Tyrosine-protein kinase JAK2	5.7	5.7	5.7	pIC50	1
Homo sapiens	Tyrosine-protein kinase JAK3	8.7	5.9	9.6	pIC50	104
Homo sapiens	Tyrosine-protein kinase JAK3	8.7	8.7	9.8	pKd	8
Homo sapiens	Tyrosine-protein kinase JAK3	9.4	9	9.7	pKi	12
Mus musculus	Tyrosine-protein kinase JAK3	6.6	5.8	7.3	pIC50	10
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	44
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	10

3EYG - chain A (model A) | Janus kinase 1

Structure information

2D & 3D views

Binding pocket waters

Binding pocket sequence

Modified residues

Orthosteric ligand

Kinase-ligand interactions

Interaction pattern search

Binding affinities