PDB-3e8c: Crystal structures of the kinase domain of PKA in complex with AT...

ID or keywords:

Entry

Database: PDB / ID: 3e8c

Title

Crystal structures of the kinase domain of PKA in complex with ATP-competitive inhibitors

Components

cAMP-dependent protein kinase catalytic subunit alpha
cAMP-dependent protein kinase inhibitor peptide

Keywords

TRANSFERASE / PKA / AKT2 / kinase / PKI / bovine / inhibitor / ATP-binding / cAMP / Lipoprotein / Myristate / Nucleotide-binding / Nucleus / Phosphoprotein / Serine/threonine-protein kinase / Protein kinase inhibitor

Function / homology

Function and homology information

CD209 (DC-SIGN) signaling / HDL assembly / Regulation of insulin secretion / Rap1 signalling / Ion homeostasis / PKA activation in glucagon signalling / DARPP-32 events / CREB1 phosphorylation through the activation of Adenylate Cyclase / GPER1 signaling / Factors involved in megakaryocyte development and platelet production ...
Similarity search - Function

Biological species

Bos taurus (cattle)

Method

X-RAY DIFFRACTION /

SYNCHROTRON / Resolution: 2.2 Å

Authors

Concha, N.O. / Elkins, P.A. / Smallwood, A. / Ward, P.

Citation

Journal: Bioorg.Med.Chem.Lett. / Year: 2009
Title: Aminofurazans as potent inhibitors of AKT kinase
Authors: Rouse, M.B. / Seefeld, M.A. / Leber, J.D. / McNulty, K.C. / Sun, L. / Miller, W.H. / Zhang, S. / Minthorn, E.A. / Concha, N.O. / Choudhry, A.E. / Schaber, M.D. / Heerding, D.A.

History

Deposition	Aug 19, 2008	Deposition site: RCSB / Processing site: RCSB
Revision 1.0	Nov 18, 2008	Provider: repository / Type: Initial release
Revision 1.1	Jul 13, 2011	Group: Advisory / Refinement description / Version format compliance
Revision 1.2	Oct 25, 2017	Group: Refinement description / Category: software Item: _software.classification / _software.contact_author ..._software.classification / _software.contact_author / _software.contact_author_email / _software.date / _software.language / _software.location / _software.name / _software.type / _software.version

Structure viewer	Molecule: MolmilJmol/JSmol

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Download

PDBx/mmCIF format	3e8c.cif.gz	444.8 KB	Display	PDBx/mmCIF format
PDB format	pdb3e8c.ent.gz	379.6 KB	Display	PDB format
PDBx/mmJSON format	3e8c.json.gz		Tree view	PDBx/mmJSON format
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Validation report

Summary document	3e8c_validation.pdf.gz	2.3 MB	Display	wwPDB validaton report
Full document	3e8c_full_validation.pdf.gz	2.3 MB	Display
Data in XML	3e8c_validation.xml.gz	85.3 KB	Display
Data in CIF	3e8c_validation.cif.gz	117 KB	Display
Arichive directory	https://data.pdbj.org/pub/pdb/validation_reports/e8/3e8c ftp://data.pdbj.org/pub/pdb/validation_reports/e8/3e8c	HTTPS FTP

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Related structure data

Related structure data	3e87C 3e88C 3e8dC 3e8eC C: citing same article (ref.)
Similar structure data	3e8e-1 4dg2-d 3e8e-3 5ol3-d 6ynt-d 1sve-d 4ujb-d 1xha-d 3e8e-6 5n23-d 3ama-d 6esa-d 6y2u-d 5i09-d 1svg-d Search similar-shape structures by Omokage search (details) Search similar-shape structures by Omokage search (details) Search similar-shape structures by Omokage search (details) Search similar-shape structures by Omokage search (details) Search similar-shape structures by Omokage search (details) Search similar-shape structures by Omokage search (details) Search similar-shape structures by Omokage search (details) Similarity search - Function & homologyF&H Search Similarity search - FunctionF&H Search Similarity search - HomologyF&H Search

Related structure data

C: citing same article (ref.)

Similar structure data

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Links

PDB pages	PDBj / wwPDB / NCBI
Related items in Molecule of the Month	#152 - Aug 2012 cAMP-dependent Protein Kinase similarity (7) #251 - Nov 2020 Adenylyl Cyclase similarity (1) #183 - Mar 2015 Phototropin similarity (7) #196 - Apr 2016 Lead Poisoning similarity (3)

Deposited unit

A: cAMP-dependent protein kinase catalytic subunit alpha

B: cAMP-dependent protein kinase catalytic subunit alpha

C: cAMP-dependent protein kinase catalytic subunit alpha

D: cAMP-dependent protein kinase catalytic subunit alpha

E: cAMP-dependent protein kinase catalytic subunit alpha

F: cAMP-dependent protein kinase catalytic subunit alpha

G: cAMP-dependent protein kinase inhibitor peptide

H: cAMP-dependent protein kinase inhibitor peptide

I: cAMP-dependent protein kinase inhibitor peptide

J: cAMP-dependent protein kinase inhibitor peptide

K: cAMP-dependent protein kinase inhibitor peptide

L: cAMP-dependent protein kinase inhibitor peptide

hetero molecules

261 kDa, 12 polymers
Search similar-shape structures of this assembly by Omokage search (details)

1

A: cAMP-dependent protein kinase catalytic subunit alpha

G: cAMP-dependent protein kinase inhibitor peptide

hetero molecules

defined by author&software
43.5 kDa, 2 polymers
Search similar-shape structures of this assembly by Omokage search (details)

2

B: cAMP-dependent protein kinase catalytic subunit alpha

H: cAMP-dependent protein kinase inhibitor peptide

hetero molecules

defined by author&software
43.5 kDa, 2 polymers
Search similar-shape structures of this assembly by Omokage search (details)

3

C: cAMP-dependent protein kinase catalytic subunit alpha

I: cAMP-dependent protein kinase inhibitor peptide

hetero molecules

defined by author&software
43.5 kDa, 2 polymers
Search similar-shape structures of this assembly by Omokage search (details)

4

D: cAMP-dependent protein kinase catalytic subunit alpha

J: cAMP-dependent protein kinase inhibitor peptide

hetero molecules

defined by author&software
43.5 kDa, 2 polymers
Search similar-shape structures of this assembly by Omokage search (details)

5

E: cAMP-dependent protein kinase catalytic subunit alpha

K: cAMP-dependent protein kinase inhibitor peptide

hetero molecules

defined by author&software
43.5 kDa, 2 polymers
Search similar-shape structures of this assembly by Omokage search (details)

6

F: cAMP-dependent protein kinase catalytic subunit alpha

L: cAMP-dependent protein kinase inhibitor peptide

hetero molecules

defined by author&software
43.5 kDa, 2 polymers
Search similar-shape structures of this assembly by Omokage search (details)

Unit cell

Length a, b, c (Å)	82.460, 96.392, 180.036
Angle α, β, γ (deg.)	90.00, 102.66, 90.00
Int Tables number	4
Space group name H-M	P12₁1

Noncrystallographic symmetry (NCS)

NCS domain:

ID	Ens-ID	Details
1	1	A
2	1	B
3	1	C
4	1	D
5	1	E
6	1	F
1	2	G
2	2	H
3	2	I
4	2	J
5	2	K
6	2	L

NCS domain segments:

Dom-ID	Component-ID	Ens-ID	Refine code	Auth asym-ID	Auth seq-ID
1	1	1	2	A	17 - 350
2	1	1	2	B	17 - 350
3	1	1	2	C	17 - 350
4	1	1	2	D	17 - 350
5	1	1	2	E	17 - 350
6	1	1	2	F	17 - 350
1	1	2	2	G	7 - 23
2	1	2	2	H	7 - 23
3	1	2	2	I	7 - 23
4	1	2	2	J	7 - 23
5	1	2	2	K	7 - 23
6	1	2	2	L	7 - 23

NCS ensembles :

ID
1
2

#1: Protein	cAMP-dependent protein kinase catalytic subunit alpha / PKA C-alpha Mass: 40786.395 Da / Num. of mol.: 6 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Bos taurus (cattle) / Gene: PKA, PRKACA / Plasmid: pDEST14 / Production host: Escherichia coli (E. coli) / Strain (production host): BL21(AI) / References: UniProt: P00517, cAMP-dependent protein kinase
#2: Protein/peptide	cAMP-dependent protein kinase inhibitor peptide / PKI-alpha / PKI inhibitor peptide Mass: 2226.411 Da / Num. of mol.: 6 / Source method: obtained synthetically Details: THE PEPTIDE WAS CHEMICALLY SYNTHESIZED. IT SOURCE 10 IS FOUND NATURALLY IN BOVINE. References: UniProt: Q3SX13
#3: Chemical	ChemComp-G96 / 4-[2-(4-amino-1,2,5-oxadiazol-3-yl)-6-{[(2R)-2-amino-3-phenylpropyl]oxy}-1-ethyl-1H-imidazo[4,5-c]pyridin-4-yl]-2-methylbut-3-yn-2-ol Mass: 461.516 Da / Num. of mol.: 6 / Source method: obtained synthetically / Formula: C₂₄H₂₇N₇O₃
#4: Water	ChemComp-HOH / water Mass: 18.015 Da / Num. of mol.: 762 / Source method: isolated from a natural source / Formula: H₂O

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Experiment

Experiment	Method: X-RAY DIFFRACTION / Number of used crystals: 1

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Sample preparation

Crystal	Density Matthews: 2.7 Å³/Da / Density % sol: 54.39 %
Crystal grow	Temperature: 273 K / Method: vapor diffusion Details: 13-17% PEG 3K-20K, 100 mM MES pH 6.5 or acetate 4.6, 1-15% methanol. Seeded, pH 4.5 - 6.5, vapor diffusion, temperature 273K PH range: 4.5 - 6.5

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Data collection

Diffraction	Mean temperature: 100 K
Diffraction source	Source: SYNCHROTRON / Site: APS / Beamline: 17-ID / Wavelength: 1 Å
Detector	Type: ADSC QUANTUM 210 / Detector: CCD / Date: Oct 1, 2005 / Details: un-focused beam
Radiation	Monochromator: GRAPHITE / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelength	Wavelength: 1 Å / Relative weight: 1
Reflection	Resolution: 2.2→50 Å / Num. obs: 137412 / % possible obs: 98.2 % / Observed criterion σ(I): 2 / Redundancy: 4.3 % / R_merge(I) obs: 0.079
Reflection shell	Resolution: 2.2→2.28 Å / Redundancy: 4.2 % / R_merge(I) obs: 0.6 / % possible all: 97.3

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Processing

Software

Name	Version	Classification
DENZO		data reduction
SCALEPACK		data scaling
REFMAC	5.2.0019	refinement
PDB_EXTRACT	3.006	data extraction
JDirector		data collection
HKL-2000		data reduction
AMoRE		phasing

Refinement

Resolution: 2.2→46.93 Å / Cor.coef. F_o:F_c: 0.929 / Cor.coef. F_o:F_c free: 0.911 / Occupancy max: 1 / Occupancy min: 0.5 / SU B: 22.439 / SU ML: 0.267 / TLS residual ADP flag: LIKELY RESIDUAL / Cross valid method: THROUGHOUT / ESU R: 0.36 / ESU R Free: 0.253 / Stereochemistry target values: MAXIMUM LIKELIHOOD / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS

	R_factor	Num. reflection	% reflection	Selection details
R_free	0.28988	6773	5 %	RANDOM
R_work	0.26365	-	-	-
obs	0.26499	127573	95.82 %	-

Solvent computation

Ion probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK

Displacement parameters

B_iso mean: 14.349 Å²

	B_aniso -1	B_aniso -2	B_aniso -3
1-	-1.65 Å²	0 Å²	-1.98 Å²
2-	-	-0.35 Å²	0 Å²
3-	-	-	1.13 Å²

Refinement step

Cycle: LAST / Resolution: 2.2→46.93 Å

	Protein	Nucleic acid	Ligand	Solvent	Total
Num. atoms	17921	0	204	762	18887

Refine LS restraints

Refine-ID	Type	Dev ideal	Dev ideal target	Number
X-RAY DIFFRACTION	r_bond_refined_d	0.007	0.022	18598
X-RAY DIFFRACTION	r_bond_other_d	0.002	0.02	12924
X-RAY DIFFRACTION	r_angle_refined_deg	1.195	1.968	25120
X-RAY DIFFRACTION	r_angle_other_deg	0.928	3	31323
X-RAY DIFFRACTION	r_dihedral_angle_1_deg	5.044	5	2169
X-RAY DIFFRACTION	r_dihedral_angle_2_deg	36.604	23.967	920
X-RAY DIFFRACTION	r_dihedral_angle_3_deg	15.535	15.05	3284
X-RAY DIFFRACTION	r_dihedral_angle_4_deg	18.049	15	107
X-RAY DIFFRACTION	r_chiral_restr	0.085	0.2	2605
X-RAY DIFFRACTION	r_gen_planes_refined	0.003	0.02	20367
X-RAY DIFFRACTION	r_gen_planes_other	0.001	0.02	3992
X-RAY DIFFRACTION	r_nbd_refined	0.176	0.2	3801
X-RAY DIFFRACTION	r_nbd_other	0.178	0.2	13177
X-RAY DIFFRACTION	r_nbtor_refined	0.176	0.2	8935
X-RAY DIFFRACTION	r_nbtor_other	0.079	0.2	9665
X-RAY DIFFRACTION	r_xyhbond_nbd_refined	0.161	0.2	813
X-RAY DIFFRACTION	r_xyhbond_nbd_other	0.072	0.2	2
X-RAY DIFFRACTION	r_metal_ion_refined
X-RAY DIFFRACTION	r_metal_ion_other
X-RAY DIFFRACTION	r_symmetry_vdw_refined	0.172	0.2	44
X-RAY DIFFRACTION	r_symmetry_vdw_other	0.238	0.2	101
X-RAY DIFFRACTION	r_symmetry_hbond_refined	0.156	0.2	18
X-RAY DIFFRACTION	r_symmetry_hbond_other
X-RAY DIFFRACTION	r_symmetry_metal_ion_refined
X-RAY DIFFRACTION	r_symmetry_metal_ion_other
X-RAY DIFFRACTION	r_mcbond_it	0.253	1.5	11357
X-RAY DIFFRACTION	r_mcbond_other	0.119	1.5	4401
X-RAY DIFFRACTION	r_mcangle_it	0.405	2	17481
X-RAY DIFFRACTION	r_scbond_it	0.519	3	8607
X-RAY DIFFRACTION	r_scangle_it	0.788	4.5	7638
X-RAY DIFFRACTION	r_rigid_bond_restr
X-RAY DIFFRACTION	r_sphericity_free
X-RAY DIFFRACTION	r_sphericity_bonded

Refine LS restraints NCS

Refine-ID: X-RAY DIFFRACTION

Ens-ID	Dom-ID	Auth asym-ID	Number	Type	Rms dev position (Å)	Weight position
1	1	A	1968	tight positional	0.03	0.05
1	2	B	1968	tight positional	0.02	0.05
1	3	C	1968	tight positional	0.02	0.05
1	4	D	1968	tight positional	0.02	0.05
1	5	E	1968	tight positional	0.02	0.05
1	6	F	1968	tight positional	0.02	0.05
2	1	G	92	tight positional	0.27	0.05
2	2	H	92	tight positional	0.06	0.05
2	3	I	92	tight positional	0.06	0.05
2	4	J	92	tight positional	0.06	0.05
2	5	K	92	tight positional	0.05	0.05
2	6	L	92	tight positional	0.06	0.05
1	1	A	2726	medium positional	0.39	0.5
1	2	B	2726	medium positional	0.44	0.5
1	3	C	2726	medium positional	0.43	0.5
1	4	D	2726	medium positional	0.42	0.5
1	5	E	2726	medium positional	0.43	0.5
1	6	F	2726	medium positional	0.37	0.5
2	1	G	123	medium positional	1.32	0.5
2	2	H	123	medium positional	0.45	0.5
2	3	I	123	medium positional	0.51	0.5
2	4	J	123	medium positional	0.41	0.5
2	5	K	123	medium positional	0.47	0.5
2	6	L	123	medium positional	0.33	0.5
1	1	A	1968	tight thermal	0.04	0.5
1	2	B	1968	tight thermal	0.04	0.5
1	3	C	1968	tight thermal	0.03	0.5
1	4	D	1968	tight thermal	0.03	0.5
1	5	E	1968	tight thermal	0.03	0.5
1	6	F	1968	tight thermal	0.03	0.5
2	1	G	92	tight thermal	0.04	0.5
2	2	H	92	tight thermal	0.04	0.5
2	3	I	92	tight thermal	0.04	0.5
2	4	J	92	tight thermal	0.02	0.5
2	5	K	92	tight thermal	0.02	0.5
2	6	L	92	tight thermal	0.05	0.5
1	1	A	2726	medium thermal	0.21	2
1	2	B	2726	medium thermal	0.23	2
1	3	C	2726	medium thermal	0.19	2
1	4	D	2726	medium thermal	0.17	2
1	5	E	2726	medium thermal	0.17	2
1	6	F	2726	medium thermal	0.17	2
2	1	G	123	medium thermal	0.17	2
2	2	H	123	medium thermal	0.2	2
2	3	I	123	medium thermal	0.25	2
2	4	J	123	medium thermal	0.14	2
2	5	K	123	medium thermal	0.12	2
2	6	L	123	medium thermal	0.15	2

LS refinement shell

Resolution: 2.197→2.254 Å / Total num. of bins used: 20

	R_factor	Num. reflection	% reflection
R_free	0.582	340	-
R_work	0.516	6623	-
obs	-	-	67.56 %

Refinement TLS params.

Method: refined / Refine-ID: X-RAY DIFFRACTION

ID	L11 (°²)	L12 (°²)	L13 (°²)	L22 (°²)	L23 (°²)	L33 (°²)	S11 (Å °)	S12 (Å °)	S13 (Å °)	S21 (Å °)	S22 (Å °)	S23 (Å °)	S31 (Å °)	S32 (Å °)	S33 (Å °)	T11 (Å²)	T12 (Å²)	T13 (Å²)	T22 (Å²)	T23 (Å²)	T33 (Å²)	Origin x (Å)	Origin y (Å)	Origin z (Å)
1	0.6021	0.207	0.2455	0.2881	0.0585	2.2118	-0.0086	-0.0379	0.0707	0.0238	-0.045	-0.0158	0.0394	0.1209	0.0536	-0.2616	0.0087	-0.0203	0.0176	-0.0077	-0.144	4.461	-9.235	29.99
2	0.9277	-0.0669	0.498	0.3261	0.0308	1.4947	-0.0033	-0.0518	-0.0318	0.0349	0.0093	-0.0213	0.115	0.0059	-0.006	-0.2815	0.0055	-0.0143	-0.0535	-0.0078	-0.1786	-32.841	-9.022	5.8
3	1.0753	0.081	0.8116	0.5841	0.2536	1.9517	-0.0213	-0.264	0.1905	0.0573	-0.1081	0.0672	-0.0219	-0.0001	0.1294	-0.2388	0.0201	-0.014	0.0422	-0.0254	-0.1313	-17.976	37.948	28.765
4	1.2108	0.0309	0.426	0.8644	0.1904	1.3047	-0.0482	-0.256	-0.0476	0.0986	0.0574	-0.0044	0.0787	-0.0668	-0.0092	-0.1846	-0.0269	-0.0382	0.1195	-0.0032	-0.1385	19.443	40.081	52.785
5	2.2928	-0.1292	1.1428	0.278	0.1272	2.7743	0.0731	-0.3293	-0.1393	0.0914	0.0782	-0.0721	0.0978	0.0858	-0.1513	-0.1759	0.0105	-0.0308	0.217	0.0107	-0.1135	-46.398	-5.535	64.35
6	1.8538	-0.5992	0.4203	0.824	0.512	3.2811	-0.2447	-0.4934	-0.0002	0.1586	0.1568	0.1574	0.0331	0.0099	0.0879	-0.1403	0.0199	0.0201	0.4218	0.0175	-0.1066	-8.951	-3.538	88.442

Refinement TLS group

ID	Refine-ID	Refine TLS-ID	Auth asym-ID	Auth seq-ID
1	X-RAY DIFFRACTION	1	A	7 - 350
2	X-RAY DIFFRACTION	1	G	5 - 22
3	X-RAY DIFFRACTION	2	B	4 - 350
4	X-RAY DIFFRACTION	2	H	5 - 24
5	X-RAY DIFFRACTION	3	C	7 - 350
6	X-RAY DIFFRACTION	3	I	5 - 24
7	X-RAY DIFFRACTION	4	D	4 - 350
8	X-RAY DIFFRACTION	4	J	5 - 23
9	X-RAY DIFFRACTION	5	E	13 - 350
10	X-RAY DIFFRACTION	5	K	5 - 24
11	X-RAY DIFFRACTION	6	F	7 - 350
12	X-RAY DIFFRACTION	6	L	6 - 24

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