KLIFS - the structural kinase database

Structure information


PDB:	4GV1
PubMed:	23394218
Release date:	2013-02-27
Resolution:	1.49 Å

Kinase:	AKT1
Family:	Akt
Group:	AGC
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 (2.5Å)


ASP rotation (xDFG.81) :	9°
PHE rotation (xDFG.82) :	1°
Activation loop position:	-4.2Å
αC-helix position:	17.3Å

G-rich loop angle:	58.4°
G-rich loop distance:	17.8Å
G-rich loop rotation:	59°

Other models from this PDB:

2D & 3D views

Binding pocket waters

The following waters were found in the defined clusters:

I1

H-bond protein

I3

H-bond ligand

H-bond protein

I5

H-bond protein

I11

H-bond protein

Binding pocket sequence

Uniprot	KLLGKGTFGKVILYAMKILHTLTENRVLQNSRPFLTALKYSCFVMEYANGGELFFHLSRLHSEKNVVYRDLKLENLMLITDFGLC
Structure:	KLLGKGTFGKVILYAMKILHTLTENRVLQNSRPFLTALKYSCFVMEYANGGELFFHLSRLHSEKNVVYRDLKLENLMLITDFGLC

Modified residues

Residue 308 (not in pocket)

Phosphorylated threonine

Orthosteric ligand

Ligand HET-code: 0XZ
Ligand Name: 4-amino-N-[(1S)-1-(4-chlorophenyl)-3-hydroxypropyl]-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carboxamide

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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
154

2 L
155

3 L
156

4 G
157

5 K
158

6 G
159

7 T
160

8 F
161

9 G
162

10 K
163

11 V
164

12 I
165

13 L
166

14 Y
176

15 A
177

16 M
178

17 K
179

18 I
180

19 L
181

20 H
194

■

αC

b.l

IV

21 T
195

22 L
196

23 T
197

24 E
198

25 N
199

26 R
200

27 V
201

28 L
202

29 Q
203

30 N
204

31 S
205

32 R
206

33 P
208

34 F
209

35 L
210

36 T
211

37 A
212

38 L
213

39 K
214

40 Y
215

■

IV

V

GK

hinge

linker

αD

αE

41 S
216

42 C
224

43 F
225

44 V
226

45 M
227

46 E
228

47 Y
229

48 A
230

49 N
231

50 G
232

51 G
233

52 E
234

53 L
235

54 F
236

55 F
237

56 H
238

57 L
239

58 S
240

59 R
241

60 L
264

■

▲

■♦

■▲

αE

VI

c.l

VII

VIII

x

61 H
265

62 S
266

63 E
267

64 K
268

65 N
269

66 V
270

67 V
271

68 Y
272

69 R
273

70 D
274

71 L
275

72 K
276

73 L
277

74 E
278

75 N
279

76 L
280

77 M
281

78 L
282

79 I
290

80 T
291

■

DFG

a.l

81 D
292

82 F
293

83 G
294

84 L
295

85 C
296

■

Interaction pattern search

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

Binding affinities

ChEMBL ID:CHEMBL2325741
Bioaffinities: 34 records for 28 kinase(s)

Species	Kinase (ChEMBL naming)	Median	Min	Max	Type	Records
Homo sapiens	AMP-activated protein kinase, alpha-1 subunit	5.7	5.7	5.7	pKd	1
Homo sapiens	AMP-activated protein kinase, gamma-1 subunit	5.6	5.6	5.6	pKd	1
Homo sapiens	AMP-activated protein kinase, gamma-2 subunit	5.6	5.6	5.6	pKd	1
Homo sapiens	cAMP-dependent protein kinase alpha-catalytic subunit	6.4	6.4	6.4	pKd	1
Homo sapiens	cAMP-dependent protein kinase beta-1 catalytic subunit	6.6	6.6	6.6	pKd	1
Homo sapiens	cGMP-dependent protein kinase 1 beta	6.5	6.5	6.5	pKd	1
Homo sapiens	Dual specificity protein kinase CLK4	6.3	6.3	6.3	pKd	1
Homo sapiens	Dual specificty protein kinase CLK1	6.3	6.3	6.3	pKd	1
Homo sapiens	Fibroblast growth factor receptor 1	6.1	6.1	6.1	pKd	1
Homo sapiens	G-protein coupled receptor kinase 2	5.3	5.3	5.3	pKd	1
Homo sapiens	LIM domain kinase 1	6.5	6.5	6.5	pKd	1
Homo sapiens	LIM domain kinase 2	6.3	6.3	6.3	pKd	1
Homo sapiens	Mitogen-activated protein kinase kinase kinase 11	5.7	5.7	5.7	pKd	1
Homo sapiens	Mitogen-activated protein kinase kinase kinase kinase 3	5.7	5.7	5.7	pKd	1
Homo sapiens	Protein kinase C alpha	5.8	5.8	5.8	pKd	1
Homo sapiens	Protein kinase C beta	5.6	5.6	5.6	pKd	1
Homo sapiens	Protein kinase C delta	5.6	5.6	5.6	pKd	1
Homo sapiens	Protein kinase C nu	5.7	5.7	5.7	pKd	1
Homo sapiens	Protein kinase C theta	5.4	5.4	5.4	pKd	1
Homo sapiens	Protein kinase N1	5.8	5.8	5.8	pKd	1
Homo sapiens	Rho-associated protein kinase 1	6.3	6.3	6.3	pIC50	1
Homo sapiens	Rho-associated protein kinase 1	6.2	6.2	6.2	pKd	1
Homo sapiens	Rho-associated protein kinase 2	7.3	7.3	7.3	pIC50	1
Homo sapiens	Rho-associated protein kinase 2	6.5	6.5	6.5	pKd	1
Homo sapiens	Serine/threonine-protein kinase AKT	7.6	7.5	8.5	pIC50	3
Homo sapiens	Serine/threonine-protein kinase AKT	5.4	5.4	5.4	pKd	1
Homo sapiens	Serine/threonine-protein kinase AKT2	8.1	8.1	8.1	pIC50	1
Homo sapiens	Serine/threonine-protein kinase AKT2	5.6	5.6	5.6	pKd	1
Homo sapiens	Serine/threonine-protein kinase AKT3	8.1	8.1	8.1	pIC50	1
Homo sapiens	Serine/threonine-protein kinase D2	5.7	5.7	5.7	pKd	1
Homo sapiens	Serine/threonine-protein kinase LATS1	4.9	4.9	4.9	pKd	1
Homo sapiens	Tyrosine-protein kinase receptor RET	6	6	6	pKd	1

4GV1 - chain A (model B) | V-akt murine thymoma viral oncogene homolog 1

Structure information

2D & 3D views

Binding pocket waters

Binding pocket sequence

Modified residues

Orthosteric ligand

Kinase-ligand interactions

Interaction pattern search

Binding affinities