KLIFS - the structural kinase database

Structure information


PDB:	5FM2
PubMed:	28009299
Release date:	2016-12-28
Resolution:	3.3 Å

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

Quality Score:	8
Missing Residues:	0
Missing Atoms:	29

DFG conformation:	in
αC-helix conformation:	in
Salt bridge K^III.17 and E^αC.24:	Yes (2.8Å)


ASP rotation (xDFG.81) :	312°
PHE rotation (xDFG.82) :	15°
Activation loop position:	-3.4Å
αC-helix position:	15.9Å

G-rich loop angle:	55.3°
G-rich loop distance:	16.8Å
G-rich loop rotation:	31.9°

2D & 3D views

Binding pocket waters

No waters were found in the defined clusters

Binding pocket sequence

Uniprot	KTLGEGEFGKVVKVAVKMLDLLSEFNVLKQVNPHVIKLYGALLIVEYAKYGSLRGFLREYLAEMKLVHRDLAARNILVISDFGLS
Structure:	KTLGEGEFGKVVKVAVKMLDLLSEFNVLKQVNPHVIKLYGALLIVEYAKYGSLRGFLREYLAEMKLVHRDLAARNILVISDFGLS

Modified residues

Residue 809 (linker.50)

Phosphorylated tyrosine

Residue 905 (not in pocket)

Phosphorylated tyrosine

Residue 909 (not in pocket)

Phosphorylated serine

Residue 928 (not in pocket)

Phosphorylated tyrosine

Orthosteric ligand

Ligand HET-code: PP1
Ligand Name: 1-TER-BUTYL-3-P-TOLYL-1H-PYRAZOLO[3,4-D]PYRIMIDIN-4-YLAMINE

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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 K
728

2 T
729

3 L
730

4 G
731

5 E
732

6 G
733

7 E
734

8 F
735

9 G
736

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:CHEMBL306380
Bioaffinities: 77 records for 60 kinase(s)

Species	Kinase (ChEMBL naming)	Median	Min	Max	Type	Records
Homo sapiens	cAMP-dependent protein kinase alpha-catalytic subunit	5.8	5.8	5.8	pKi	1
Homo sapiens	Casein kinase I alpha	5.5	5.5	5.5	pKi	1
Homo sapiens	Casein kinase I delta	6.8	6.8	6.8	pIC50	1
Homo sapiens	Casein kinase I delta	6.7	6.7	6.7	pKi	1
Homo sapiens	c-Jun N-terminal kinase 2	5.6	5.6	5.6	pKi	1
Homo sapiens	Dual specificity protein kinase CLK2	5.4	5.4	5.4	pKi	1
Homo sapiens	Dual specificity protein kinase CLK4	6.2	6.2	6.2	pKi	1
Homo sapiens	Ephrin type-A receptor 2	6.9	6.9	6.9	pKi	1
Homo sapiens	Epidermal growth factor receptor erbB1	6.7	6.7	6.7	pKi	2
Homo sapiens	Fibroblast growth factor receptor 1	6.5	6.5	6.5	pKi	1
Homo sapiens	Fibroblast growth factor receptor 3	5.9	5.9	5.9	pKi	1
Homo sapiens	Insulin receptor	5.4	5.4	5.4	pKi	1
Homo sapiens	Interleukin-1 receptor-associated kinase 4	5	5	5	pKi	1
Homo sapiens	LIM domain kinase 1	6.4	6.4	6.4	pKi	1
Homo sapiens	Macrophage colony stimulating factor receptor	6.2	6.2	6.2	pKi	1
Homo sapiens	MAP kinase p38 alpha	5.6	5.6	6	pIC50	2
Homo sapiens	MAP/microtubule affinity-regulating kinase 2	5.6	5.6	5.6	pKi	1
Homo sapiens	Mitogen-activated protein kinase kinase kinase kinase 4	5.8	5.8	5.8	pKi	1
Homo sapiens	Mixed lineage kinase 7	5.3	5.3	5.3	pKi	1
Homo sapiens	Neurotrophic tyrosine kinase receptor type 2	6.5	6.5	6.5	pKi	1
Homo sapiens	NT-3 growth factor receptor	6.5	6.5	6.5	pKi	1
Homo sapiens	Platelet-derived growth factor receptor alpha	6.2	6.2	6.2	pIC50	1
Homo sapiens	Protein kinase C nu	5.5	5.5	5.5	pKi	1
Homo sapiens	Proto-oncogene tyrosine-protein kinase ROS	5.7	5.7	5.7	pKi	1
Homo sapiens	Receptor protein-tyrosine kinase erbB-2	6.2	6.2	6.2	pKi	1
Homo sapiens	Receptor protein-tyrosine kinase erbB-4	6.7	6.7	6.7	pKi	1
Homo sapiens	Rho-associated protein kinase 1	5.3	5.3	5.3	pKi	1
Homo sapiens	Rho-associated protein kinase 2	5.5	5.5	5.5	pKi	1
Homo sapiens	Ribosomal protein S6 kinase 1	6.3	6.3	6.3	pKi	1
Homo sapiens	Ribosomal protein S6 kinase alpha 3	6.8	6.8	6.8	pKi	2
Homo sapiens	Serine/threonine-protein kinase 2	5.8	5.8	5.8	pKi	1
Homo sapiens	Serine/threonine-protein kinase AKT3	5.1	5.1	5.1	pKi	1
Homo sapiens	Serine/threonine-protein kinase Aurora-B	5.9	5.9	5.9	pKi	1
Homo sapiens	Serine/threonine-protein kinase D2	5.4	5.4	5.4	pKi	1
Homo sapiens	Serine/threonine-protein kinase MRCK-A	5.2	5.2	5.2	pKi	1
Homo sapiens	Serine/threonine-protein kinase MST2	5.4	5.4	5.4	pKi	1
Homo sapiens	Serine/threonine-protein kinase mTOR	5	5	5	pIC50	1
Homo sapiens	Serine/threonine-protein kinase PLK4	6	6	6	pKi	1
Homo sapiens	Serine/threonine-protein kinase RIPK2	7.6	7.6	7.6	pIC50	1
Homo sapiens	Serine/threonine-protein kinase TAO1	5.7	5.7	5.7	pKi	1
Homo sapiens	Stem cell growth factor receptor	5.9	5.9	5.9	pIC50	1
Homo sapiens	Stem cell growth factor receptor	6.3	6.3	6.3	pKi	1
Homo sapiens	Tyrosine-protein kinase ABL	6.8	6.8	6.8	pIC50	1
Homo sapiens	Tyrosine-protein kinase ABL	6.6	6.6	6.6	pKi	1
Homo sapiens	Tyrosine-protein kinase BLK	8	8	8	pKi	1
Homo sapiens	Tyrosine-protein kinase BRK	8.1	8.1	8.1	pKi	1
Homo sapiens	Tyrosine-protein kinase BTK	7.2	7.2	7.2	pKi	1
Homo sapiens	Tyrosine-protein kinase CSK	6.2	6.2	6.2	pIC50	1
Homo sapiens	Tyrosine-protein kinase FRK	8.5	8.5	8.5	pKi	1
Homo sapiens	Tyrosine-protein kinase FYN	7.6	7.6	8	pIC50	2
Homo sapiens	Tyrosine-protein kinase FYN	7.5	7.5	7.5	pKi	1
Homo sapiens	Tyrosine-protein kinase LCK	6.8	6.6	8.3	pIC50	3
Homo sapiens	Tyrosine-protein kinase LCK	7.2	7.2	7.2	pKi	2
Mus musculus	Tyrosine-protein kinase LCK	7.4	7.4	7.4	pIC50	1
Homo sapiens	Tyrosine-protein kinase Lyn	7.7	7.7	7.7	pKi	1
Homo sapiens	Tyrosine-protein kinase receptor FLT3	5.7	5.7	5.7	pKi	1
Homo sapiens	Tyrosine-protein kinase receptor RET	8	8	8	pIC50	1
Homo sapiens	Tyrosine-protein kinase receptor RET	8	8	8	pKi	1
Gallus gallus	Tyrosine-protein kinase SRC	7.3	7.3	7.3	pIC50	1
Homo sapiens	Tyrosine-protein kinase SRC	7.8	6.8	8.3	pIC50	3
Homo sapiens	Tyrosine-protein kinase SRC	7.4	7.4	7.4	pKi	1
Homo sapiens	Tyrosine-protein kinase Srms	6.3	6.3	6.3	pKi	1
Homo sapiens	Tyrosine-protein kinase TIE-2	5.2	5.2	5.2	pIC50	1
Homo sapiens	Tyrosine-protein kinase YES	7.4	7.4	7.4	pIC50	1
Homo sapiens	Vascular endothelial growth factor receptor 1	6.8	6.8	6.8	pKi	1
Homo sapiens	Vascular endothelial growth factor receptor 2	5.8	5.8	5.8	pIC50	1
Homo sapiens	Vascular endothelial growth factor receptor 2	6.7	6.7	6.7	pKi	1
Homo sapiens	Vascular endothelial growth factor receptor 3	6.2	6.2	6.2	pKi	1

5FM2 - chain A | Ret proto-oncogene

Structure information

2D & 3D views

Binding pocket waters

Binding pocket sequence

Modified residues

Orthosteric ligand

Kinase-ligand interactions

Interaction pattern search

Binding affinities