KLIFS - the structural kinase database

Structure information


PDB:	2X2M
PubMed:	20117004
Release date:	2010-02-09
Resolution:	2.5 Å

Kinase:	RET
Family:	Ret
Group:	TK
Species:	HUMAN

Quality Score:	6.9
Missing Residues:	4
Missing Atoms:	15

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


ASP rotation (xDFG.81) :	359°
PHE rotation (xDFG.82) :	16°
Activation loop position:	-3.4Å
αC-helix position:	16.7Å

G-rich loop angle:	-
G-rich loop distance:	-
G-rich loop rotation:	-

Other models from this PDB:

2D & 3D views

Binding pocket waters

The following waters were found in the defined clusters:

I5

H-bond protein

Binding pocket sequence

Uniprot	KTLGEGEFGKVVKVAVKMLDLLSEFNVLKQVNPHVIKLYGALLIVEYAKYGSLRGFLREYLAEMKLVHRDLAARNILVISDFGLS
Structure:	KTLGE____KVVKVAVKMLDLLSEFNVLKQVNPHVIKLYGALLIVEYAKYGSLRGFLREYLAEMKLVHRDLAARNILVISDFGLS

Modified residues

Residue 905 (not in pocket)

Phosphorylated tyrosine

Orthosteric ligand

Ligand HET-code: X2M
Ligand Name: (3Z)-3-[(3,5-DIMETHYL-1H-PYRROL-2-YL)METHYLIDENE]-1,3-DIHYDRO-2H-INDOL-2-ONE

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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 K
728

2 T
729

3 L
730

4 G
731

5 E
732

6 _
_

7 _
_

8 _
_

9 _
_

10 K
737

11 V
738

12 V
739

13 K
740

14 V
755

15 A
756

16 V
757

17 K
758

18 M
759

19 L
760

20 D
771

■

αC

b.l

IV

21 L
772

22 L
773

23 S
774

24 E
775

25 F
776

26 N
777

27 V
778

28 L
779

29 K
780

30 Q
781

31 V
782

32 N
783

33 P
785

34 H
786

35 V
787

36 I
788

37 K
789

38 L
790

39 Y
791

40 G
792

■

IV

V

GK

hinge

linker

αD

αE

41 A
793

42 L
801

43 L
802

44 I
803

45 V
804

46 E
805

47 Y
806

48 A
807

49 K
808

50 Y
809

51 G
810

52 S
811

53 L
812

54 R
813

55 G
814

56 F
815

57 L
816

58 R
817

59 E
818

60 Y
864

■

▲

■

■▲

■

αE

VI

c.l

VII

VIII

x

61 L
865

62 A
866

63 E
867

64 M
868

65 K
869

66 L
870

67 V
871

68 H
872

69 R
873

70 D
874

71 L
875

72 A
876

73 A
877

74 R
878

75 N
879

76 I
880

77 L
881

78 V
882

79 I
890

80 S
891

■

DFG

a.l

81 D
892

82 F
893

83 G
894

84 L
895

85 S
896

Interaction pattern search

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

Binding affinities

ChEMBL ID:CHEMBL276711
Bioaffinities: 71 records for 16 kinase(s)

Species	Kinase (ChEMBL naming)	Median	Min	Max	Type	Records
Homo sapiens	ALK tyrosine kinase receptor	5.7	5.7	5.9	pIC50	2
Homo sapiens	Fibroblast growth factor receptor 1	5.2	4.3	5.4	pIC50	4
Homo sapiens	Macrophage colony stimulating factor receptor	7.1	7.1	7.1	pIC50	1
Homo sapiens	Platelet-derived growth factor receptor alpha	6.7	6.7	6.7	pIC50	1
Homo sapiens	Platelet-derived growth factor receptor beta	5.3	4.4	7.2	pIC50	12
Homo sapiens	Stem cell growth factor receptor	6.4	6.2	7.5	pIC50	3
Homo sapiens	Tyrosine-protein kinase ABL	5	5	5	pIC50	1
Homo sapiens	Tyrosine-protein kinase receptor FLT3	6.8	6.8	6.8	pIC50	1
Homo sapiens	Tyrosine-protein kinase receptor RET	6.8	6.8	6.8	pIC50	1
Homo sapiens	Tyrosine-protein kinase SRC	4.8	4.8	4.8	pIC50	1
Homo sapiens	Tyrosine-protein kinase ZAP-70	4.7	4.7	4.7	pIC50	1
Homo sapiens	Vascular endothelial growth factor receptor 1	7.4	5.5	8.1	pIC50	4
Mus musculus	Vascular endothelial growth factor receptor 1	6	6	6	pIC50	1
Homo sapiens	Vascular endothelial growth factor receptor 2	5.9	4.9	7.9	pIC50	35
Mus musculus	Vascular endothelial growth factor receptor 2	6	6	6	pIC50	1
Homo sapiens	Vascular endothelial growth factor receptor 3	6.3	6.3	7.3	pIC50	2

2X2M - chain B | Ret proto-oncogene