PDB-8wdo: Crystal structure of PDE4D complexed with DCN

ID or keywords:

Entry

Database: PDB / ID: 8wdo

Title

Crystal structure of PDE4D complexed with DCN

Components

cAMP-specific 3',5'-cyclic phosphodiesterase 4D

Keywords

HYDROLASE / PDE4D / Complex / Inhibitor

Function / homology

Function and homology information

signaling receptor regulator activity / negative regulation of heart contraction / negative regulation of relaxation of cardiac muscle / 3',5'-cyclic-AMP phosphodiesterase / positive regulation of interleukin-5 production / negative regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway / establishment of endothelial barrier / regulation of cardiac muscle cell contraction / beta-2 adrenergic receptor binding / regulation of calcium ion transmembrane transport via high voltage-gated calcium channel ...
Similarity search - Function

Biological species

Homo sapiens (human)

Method

X-RAY DIFFRACTION /

SYNCHROTRON /

MOLECULAR REPLACEMENT / Resolution: 1.67 Å

Authors

Liu, J.Y. / Li, M.J. / Xu, Y.C.

Funding support

1items

Citation

Journal: J.Med.Chem. / Year: 2024
Title: Identification of Dihydrobenzofuran Neolignans as Novel PDE4 Inhibitors and Evaluation of Antiatopic Dermatitis Efficacy in DNCB-Induced Mice Model.
Authors: Gu, C. / Liu, J. / Qian, F. / Yu, W. / Huang, D. / Shen, J. / Feng, C. / Chen, K. / Li, Y. / Jiang, X. / Xu, Y. / Zhang, L.

History

Deposition	Sep 15, 2023	Deposition site: PDBJ / Processing site: PDBJ
Revision 1.0	Aug 28, 2024	Provider: repository / Type: Initial release

Structure viewer	Molecule: MolmilJmol/JSmol

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Download

PDBx/mmCIF format	8wdo.cif.gz	275.9 KB	Display	PDBx/mmCIF format
PDB format	pdb8wdo.ent.gz	223.6 KB	Display	PDB format
PDBx/mmJSON format	8wdo.json.gz		Tree view	PDBx/mmJSON format
Others	Other downloads

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Validation report

Arichive directory	https://data.pdbj.org/pub/pdb/validation_reports/wd/8wdo ftp://data.pdbj.org/pub/pdb/validation_reports/wd/8wdo	HTTPS FTP

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Related structure data

Related structure data	8wdnC C: citing same article (ref.)
Similar structure data	Similarity search - Function & homologyF&H Search Similarity search - FunctionF&H Search Similarity search - HomologyF&H Search

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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 (8) #44 - Aug 2003 Calmodulin similarity (1) #196 - Apr 2016 Lead Poisoning similarity (1) #28 - Apr 2002 Anthrax Toxin similarity (1)

Deposited unit

A: cAMP-specific 3',5'-cyclic phosphodiesterase 4D

B: cAMP-specific 3',5'-cyclic phosphodiesterase 4D

hetero molecules

81.3 kDa, 2 polymers
Search similar-shape structures of this assembly by Omokage search (details)

1

Idetical with deposited unit
defined by author
Evidence: gel filtration

Unit cell

Length a, b, c (Å)	57.504, 80.027, 163.152
Angle α, β, γ (deg.)	90.00, 90.00, 90.00
Int Tables number	19
Space group name H-M	P2₁2₁2₁

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Protein , 1 types, 2 molecules AB

#1: Protein	cAMP-specific 3',5'-cyclic phosphodiesterase 4D / PDE4D / DPDE3 / PDE43 Mass: 40096.355 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: PDE4D, DPDE3 / Production host: Escherichia coli BL21(DE3) (bacteria) / Strain (production host): BL21(DE3) References: UniProt: Q08499, 3',5'-cyclic-AMP phosphodiesterase

#1: Protein

cAMP-specific 3',5'-cyclic phosphodiesterase 4D / PDE4D / DPDE3 / PDE43

Mass: 40096.355 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.)

Homo sapiens (human) / Gene: PDE4D, DPDE3 / Production host:

Escherichia coli BL21(DE3) (bacteria) / Strain (production host): BL21(DE3)
References: UniProt: Q08499, 3',5'-cyclic-AMP phosphodiesterase

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Non-polymers , 5 types, 141 molecules

#2: Chemical	ChemComp-MG / MAGNESIUM ION Mass: 24.305 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: Mg
#3: Chemical	ChemComp-ZN / ZINC ION Mass: 65.409 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: Zn
#4: Chemical	ChemComp-W8O / 3-[(2~{S},3~{R})-2-(3,4-dimethoxyphenyl)-3-(hydroxymethyl)-7-methoxy-2,3-dihydro-1-benzofuran-5-yl]propan-1-ol Mass: 374.428 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C₂₁H₂₆O₆ / Feature type: SUBJECT OF INVESTIGATION
#5: Chemical	ChemComp-EDO / 1,2-ETHANEDIOL / ETHYLENE GLYCOL Mass: 62.068 Da / Num. of mol.: 3 / Source method: obtained synthetically / Formula: C₂H₆O₂
#6: Water	ChemComp-HOH / water Mass: 18.015 Da / Num. of mol.: 132 / Source method: isolated from a natural source / Formula: H₂O

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Details

Has ligand of interest	Y

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Experiment

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

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Sample preparation

Crystal	Density Matthews: 2.34 Å³/Da / Density % sol: 47.45 %
Crystal grow	Temperature: 277 K / Method: vapor diffusion, hanging drop / pH: 7 Details: 0.1 M HEPES, 0.2 M MgCl2, 10 % (v/v) Isopropanol, 30 % (v/v) Ethylene glycol, 18 % (w/v) PEG 3350

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Data collection

Diffraction	Mean temperature: 100 K / Serial crystal experiment: N
Diffraction source	Source: SYNCHROTRON / Site: SSRF / Beamline: BL02U1 / Wavelength: 0.9738 Å
Detector	Type: DECTRIS EIGER2 S 9M / Detector: PIXEL / Date: Aug 2, 2022
Radiation	Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelength	Wavelength: 0.9738 Å / Relative weight: 1
Reflection	Resolution: 1.67→40.79 Å / Num. obs: 85748 / % possible obs: 96.76 % / Redundancy: 2 % / CC_1/2: 0.999 / Net I/σ(I): 15.7
Reflection shell	Resolution: 1.67→1.73 Å / Num. unique obs: 8602 / CC_1/2: 0.801

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Processing

Software

Name	Version	Classification
PHENIX	1.17.1_3660	refinement
XDS		data reduction
PHASER		phasing
SCALA		data scaling

Refinement

Method to determine structure:

MOLECULAR REPLACEMENT / Resolution: 1.67→40.79 Å / SU ML: 0.19 / Cross valid method: THROUGHOUT / σ(F): 1.37 / Phase error: 21.64 / Stereochemistry target values: ML

	R_factor	Num. reflection	% reflection
R_free	0.226	4200	4.9 %
R_work	0.1973	-	-
obs	0.1987	85748	96.78 %

Solvent computation

Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL

Refinement step

Cycle: LAST / Resolution: 1.67→40.79 Å

	Protein	Nucleic acid	Ligand	Solvent	Total
Num. atoms	5152	0	70	132	5354

Refine LS restraints

Refine-ID	Type	Dev ideal	Number
X-RAY DIFFRACTION	f_bond_d	0.009	5326
X-RAY DIFFRACTION	f_angle_d	0.92	7248
X-RAY DIFFRACTION	f_dihedral_angle_d	6.808	737
X-RAY DIFFRACTION	f_chiral_restr	0.053	844
X-RAY DIFFRACTION	f_plane_restr	0.006	924

LS refinement shell

Resolution (Å)	R_factor R_free	Num. reflection R_free	R_factor R_work	Num. reflection R_work	Refine-ID	% reflection obs (%)
1.67-1.69	0.2976	164	0.2721	2702	X-RAY DIFFRACTION	99
1.69-1.71	0.2683	138	0.2589	2763	X-RAY DIFFRACTION	99
1.71-1.73	0.2781	128	0.2418	2731	X-RAY DIFFRACTION	99
1.73-1.75	0.2853	146	0.241	2776	X-RAY DIFFRACTION	99
1.75-1.77	0.274	134	0.2278	2727	X-RAY DIFFRACTION	99
1.77-1.8	0.2815	155	0.2174	2773	X-RAY DIFFRACTION	99
1.8-1.82	0.2609	143	0.2206	2732	X-RAY DIFFRACTION	99
1.82-1.85	0.2465	144	0.2234	2775	X-RAY DIFFRACTION	99
1.85-1.88	0.2318	145	0.2149	2707	X-RAY DIFFRACTION	99
1.88-1.91	0.2593	150	0.2188	2782	X-RAY DIFFRACTION	100
1.91-1.94	0.2631	85	0.2209	1809	X-RAY DIFFRACTION	65
1.94-1.98	0.2862	151	0.2168	2784	X-RAY DIFFRACTION	100
1.98-2.01	0.2559	163	0.2068	2747	X-RAY DIFFRACTION	99
2.01-2.06	0.2585	142	0.2057	2795	X-RAY DIFFRACTION	100
2.06-2.1	0.2279	108	0.197	2092	X-RAY DIFFRACTION	75
2.1-2.15	0.2208	129	0.198	2784	X-RAY DIFFRACTION	100
2.15-2.2	0.1992	145	0.1919	2794	X-RAY DIFFRACTION	100
2.2-2.26	0.2391	92	0.2012	2320	X-RAY DIFFRACTION	82
2.26-2.33	0.2607	136	0.203	2821	X-RAY DIFFRACTION	100
2.33-2.4	0.2359	144	0.193	2814	X-RAY DIFFRACTION	100
2.4-2.49	0.2604	145	0.196	2773	X-RAY DIFFRACTION	100
2.49-2.59	0.2232	133	0.1979	2844	X-RAY DIFFRACTION	100
2.59-2.71	0.2233	141	0.1985	2796	X-RAY DIFFRACTION	100
2.71-2.85	0.222	154	0.2003	2811	X-RAY DIFFRACTION	100
2.85-3.03	0.2336	160	0.1993	2839	X-RAY DIFFRACTION	100
3.03-3.26	0.2391	130	0.2103	2838	X-RAY DIFFRACTION	100
3.26-3.59	0.2063	129	0.1942	2631	X-RAY DIFFRACTION	92
3.59-4.11	0.2329	156	0.188	2870	X-RAY DIFFRACTION	100
4.11-5.18	0.1909	156	0.1754	2889	X-RAY DIFFRACTION	100
5.18-40.79	0.1951	154	0.1854	3029	X-RAY DIFFRACTION	99

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	2.8532	0.2147	0.3822	4.2924	-0.9657	2.3915	0.1123	0.4701	0.3669	-0.7801	0.0394	0.2747	-0.6072	-0.3227	-0.1193	0.4984	0.1082	0.0098	0.3671	0.0403	0.2515	10.7433	91.9977	13.3361
2	1.332	-0.433	-0.493	2.6595	0.8752	2.6673	0.156	0.118	0.2204	-0.3134	-0.1428	0.2859	-0.4735	-0.4599	-0.0026	0.2006	0.076	0.0075	0.2109	0.0128	0.2021	8.041	91.363	27.3236
3	2.2358	-0.6343	0.0061	0.9586	-0.3732	3.7375	-0.0336	0.0401	0.0613	0.0282	0.0699	-0.3248	-0.0739	0.6291	-0.0461	0.1747	-0.024	0.017	0.2394	-0.0231	0.2779	28.8906	85.8889	38.9262
4	3.2741	-1.6133	0.2015	2.992	-0.1502	1.3872	0.0829	-0.0848	0.168	0.0386	-0.0272	0.0706	-0.4423	-0.1493	-0.037	0.2746	0.0223	0.061	0.2236	-0.0108	0.2248	12.9271	96.4556	38.3059
5	8.4208	-3.3576	-2.1424	4.5296	1.5607	3.8806	-0.1436	-0.0754	-0.1629	0.2343	-0.0205	0.2848	-0.1292	-0.4099	0.1478	0.1857	0.0006	0.0327	0.2479	0.0298	0.226	7.7833	87.6098	41.5457
6	4.2005	0.6563	0.0672	2.5521	0.3144	1.5908	0.0112	0.0401	0.0336	0.2209	-0.0492	0.5145	0.3437	-0.4964	0.0412	0.2871	-0.0904	0.0701	0.3298	0.0192	0.3442	5.4109	69.6914	35.3351
7	2.0452	-0.2849	-1.8921	1.182	0.8201	4.7354	-0.0354	-0.0704	-0.1599	0.0841	-0.0808	0.2564	0.2459	-0.3403	0.1006	0.1771	-0.0411	0.0048	0.2109	0.0181	0.2901	9.9286	77.2169	30.5318
8	4.5858	-0.076	2.6661	2.1565	0.2528	4.3416	0.1129	0.1387	0.1273	-0.2972	-0.0143	-0.3598	-0.0319	0.7707	-0.0598	0.2218	0.0057	0.1116	0.2806	0.0005	0.2769	29.9306	81.5834	20.7238
9	2.9986	1.3305	1.7318	2.0799	1.2591	3.0126	0.0454	-0.0819	-0.1218	0.0458	0.1794	-0.5047	0.4057	0.8585	-0.1805	0.2344	0.0999	0.0444	0.407	-0.011	0.4037	33.0872	72.9426	24.1254
10	3.1307	0.1555	-1.5069	2.5302	-0.2124	5.1793	-0.1101	0.2731	-0.4327	-0.1549	-0.178	0.1334	0.7695	-0.4753	0.3264	0.2798	-0.0469	0.008	0.1666	-0.0347	0.2376	13.3809	68.5625	18.833
11	1.3289	0.1198	-0.4271	1.5036	0.0739	1.3189	-0.3488	-0.7584	-0.0133	0.3608	0.4151	-0.4552	0.5435	1.3349	-0.0679	0.4483	0.3756	-0.059	0.8524	-0.1083	0.3603	35.3938	83.708	69.5462
12	1.2077	-0.2647	0.1022	2.1797	0.2365	3.0476	-0.0492	0.041	0.2068	0.0001	0.2055	-0.3911	-0.0651	0.3148	-0.1465	0.1531	0.0211	0.0159	0.219	-0.0474	0.2292	26.1331	90.3313	54.3741
13	1.906	-0.822	0.1894	2.5182	-0.1613	0.2646	-0.5257	-0.0653	-0.4855	0.3435	0.2661	0.0937	1.1578	0.1146	0.2625	0.7939	0.1587	0.1606	0.2683	-0.0321	0.3475	24.4646	69.9967	59.129
14	1.617	-0.3023	-0.7216	2.1259	1.0502	2.7654	-0.636	-0.2194	-0.3504	-0.4063	0.1215	-0.1514	0.8172	0.0478	0.4725	0.9448	0.5061	0.3441	0.0528	-0.1731	0.1809	23.6317	74.3213	65.3507
15	3.1656	-1.6429	1.3147	3.1018	-1.5885	2.9415	-0.1097	-0.201	0.3867	0.3537	0.3759	-0.0002	-0.692	-0.3556	-0.1619	0.4165	0.2039	0.047	0.3787	-0.0372	0.3152	14.0539	94.2807	72.0393
16	1.3958	-0.6296	0.7374	3.231	-2.3183	3.6672	-0.0023	0.5524	0.2772	0.1537	-0.0723	0.1721	-0.1128	-0.9137	0.0456	0.4281	0.1604	0.0666	0.4599	0.0348	0.3094	5.9095	89.047	71.7229
17	1.8793	-0.4922	-0.0915	1.4505	1.2088	2.6024	-0.4991	-0.5356	-0.4388	-0.2055	0.1046	-0.038	1.3813	0.3987	0.3856	1.0465	0.2826	0.216	0.2466	0.1064	0.3474	15.5623	73.2935	78.0266

Refinement TLS group

ID	Refine-ID	Refine TLS-ID	Selection details
1	X-RAY DIFFRACTION	1	chain 'A' and (resid 88 through 116 )
2	X-RAY DIFFRACTION	2	chain 'A' and (resid 117 through 199 )
3	X-RAY DIFFRACTION	3	chain 'A' and (resid 200 through 227 )
4	X-RAY DIFFRACTION	4	chain 'A' and (resid 228 through 253 )
5	X-RAY DIFFRACTION	5	chain 'A' and (resid 254 through 271 )
6	X-RAY DIFFRACTION	6	chain 'A' and (resid 272 through 302 )
7	X-RAY DIFFRACTION	7	chain 'A' and (resid 303 through 325 )
8	X-RAY DIFFRACTION	8	chain 'A' and (resid 326 through 349 )
9	X-RAY DIFFRACTION	9	chain 'A' and (resid 350 through 375 )
10	X-RAY DIFFRACTION	10	chain 'A' and (resid 376 through 411 )
11	X-RAY DIFFRACTION	11	chain 'B' and (resid 88 through 199 )
12	X-RAY DIFFRACTION	12	chain 'B' and (resid 200 through 253 )
13	X-RAY DIFFRACTION	13	chain 'B' and (resid 254 through 302 )
14	X-RAY DIFFRACTION	14	chain 'B' and (resid 303 through 325 )
15	X-RAY DIFFRACTION	15	chain 'B' and (resid 326 through 350 )
16	X-RAY DIFFRACTION	16	chain 'B' and (resid 351 through 375 )
17	X-RAY DIFFRACTION	17	chain 'B' and (resid 376 through 411 )

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