KLIFS - the structural kinase database

Structure information


PDB:	4RA4
PubMed:	25254961
Release date:	2014-10-08
Resolution:	2.63 Å

Kinase:	PRKCA (PKCa)
Family:	PKC
Group:	AGC
Species:	HUMAN

Quality Score:	9.6
Missing Residues:	0
Missing Atoms:	4

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


ASP rotation (xDFG.81) :	2°
PHE rotation (xDFG.82) :	13°
Activation loop position:	-4Å
αC-helix position:	17.5Å

G-rich loop angle:	58.5°
G-rich loop distance:	18.3Å
G-rich loop rotation:	39.9°

2D & 3D views

Binding pocket waters

The following waters were found in the defined clusters:

I5

H-bond protein

Binding pocket sequence

Uniprot	MVLGKGSFGKVMLYAIKILCTMVEKRVLALLDPFLTQLHSCYFVMEYVNGGDLMYHIQQFLHKRGIIYRDLKLDNVMLIADFGMC
Structure:	MVLGKGSFGKVMLYAIKILCTMVEKRVLALLDPFLTQLHSCYFVMEYVNGGDLMYHIQQFLHKRGIIYRDLKLDNVMLIADFGMC

Modified residues

Residue 497 (not in pocket)

Phosphorylated threonine

Residue 638 (not in pocket)

Phosphorylated threonine

Residue 657 (not in pocket)

Phosphorylated serine

Orthosteric ligand

Ligand HET-code: 3KZ
Ligand Name: (1R)-9-[(3S,4S)-1,3-dimethylpiperidin-4-yl]-8-(2-fluorophenyl)-1-methyl-3,5-dihydro[1,2,4]triazino[3,4-c][1,4]benzoxazin-2(1H)-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 M
343

2 V
344

3 L
345

4 G
346

5 K
347

6 G
348

7 S
349

8 F
350

9 G
351

10 K
352

11 V
353

12 M
354

13 L
355

14 Y
365

15 A
366

16 I
367

17 K
368

18 I
369

19 L
370

20 C
383

■

■♦

■

αC

b.l

IV

21 T
384

22 M
385

23 V
386

24 E
387

25 K
388

26 R
389

27 V
390

28 L
391

29 A
392

30 L
393

31 L
394

32 D
395

33 P
398

34 F
399

35 L
400

36 T
401

37 Q
402

38 L
403

39 H
404

40 S
405

■

IV

V

GK

hinge

linker

αD

αE

41 C
406

42 Y
414

43 F
415

44 V
416

45 M
417

46 E
418

47 Y
419

48 V
420

49 N
421

50 G
422

51 G
423

52 D
424

53 L
425

54 M
426

55 Y
427

56 H
428

57 I
429

58 Q
430

59 Q
431

60 F
453

■

▲

■

■▲

αE

VI

c.l

VII

VIII

x

61 L
454

62 H
455

63 K
456

64 R
457

65 G
458

66 I
459

67 I
460

68 Y
461

69 R
462

70 D
463

71 L
464

72 K
465

73 L
466

74 D
467

75 N
468

76 V
469

77 M
470

78 L
471

79 I
479

80 A
480

■

DFG

a.l

81 D
481

82 F
482

83 G
483

84 M
484

85 C
485

■▲●

Interaction pattern search

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

Binding affinities

ChEMBL ID:CHEMBL3355124
Bioaffinities: 1 record for 1 kinase(s)

Species	Kinase (ChEMBL naming)	Median	Min	Max	Type	Records
Homo sapiens	Protein kinase C theta	7.8	7.8	7.8	pIC50	1

4RA4 - chain A | Protein kinase C alpha