PDB-6w58: hPGDS complexed with an aza-quinoline

ID or keywords:

Entry

Database: PDB / ID: 6w58

Title

hPGDS complexed with an aza-quinoline

Components

Hematopoietic prostaglandin D synthase

Keywords

HYDROLASE / Glutathione S-transferase

Function / homology

Function and homology information

prostaglandin-D synthase / prostaglandin-D synthase activity / negative regulation of male germ cell proliferation / Synthesis of Prostaglandins (PG) and Thromboxanes (TX) / Glutathione conjugation / prostaglandin biosynthetic process / prostaglandin metabolic process / glutathione transferase / glutathione transferase activity / glutathione metabolic process ...
Similarity search - Function

Biological species

Homo sapiens (human)

Method

X-RAY DIFFRACTION /

SYNCHROTRON /

MOLECULAR REPLACEMENT / Resolution: 2.395 Å

Authors

Elkins, P.A. / Ward, P.

Citation

Journal: Bioorg.Med.Chem. / Year: 2020
Title: The exploration of aza-quinolines as hematopoietic prostaglandin D synthase (H-PGDS) inhibitors with low brain exposure.
Authors: Cadilla, R. / Deaton, D.N. / Do, Y. / Elkins, P.A. / Ennulat, D. / Guss, J.H. / Holt, J. / Jeune, M.R. / King, A.G. / Klapwijk, J.C. / Kramer, H.F. / Kramer, N.J. / Laffan, S.B. / Masuria, P. ...

History

Deposition	Mar 12, 2020	Deposition site: RCSB / Processing site: RCSB
Revision 1.0	Nov 4, 2020	Provider: repository / Type: Initial release
Revision 1.1	Mar 6, 2024	Group: Data collection / Database references / Category: chem_comp_atom / chem_comp_bond / database_2 Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession
Revision 1.2	Apr 3, 2024	Group: Refinement description / Category: pdbx_initial_refinement_model

Structure viewer	Molecule: MolmilJmol/JSmol

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Download

PDBx/mmCIF format	6w58.cif.gz	175.8 KB	Display	PDBx/mmCIF format
PDB format	pdb6w58.ent.gz	140.1 KB	Display	PDB format
PDBx/mmJSON format	6w58.json.gz		Tree view	PDBx/mmJSON format
Others	Other downloads

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Validation report

Summary document	6w58_validation.pdf.gz	1 MB	Display	wwPDB validaton report
Full document	6w58_full_validation.pdf.gz	1 MB	Display
Data in XML	6w58_validation.xml.gz	16.7 KB	Display
Data in CIF	6w58_validation.cif.gz	22 KB	Display
Arichive directory	https://data.pdbj.org/pub/pdb/validation_reports/w5/6w58 ftp://data.pdbj.org/pub/pdb/validation_reports/w5/6w58	HTTPS FTP

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Related structure data

Related structure data	6w8hC C: citing same article (ref.)
Similar structure data	4ee0-d 6w8h-d 6n4e-1 3ee2-d 4edz-1 5yx1-2 7dax-d 5aiv-1 2vcq-1 5aix-2 Search similar-shape structures by Omokage search (details) 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	#212 - Aug 2017 Glutathione Transferases similarity (11) #255 - Mar 2021 Cisplatin and DNA similarity (11) #92 - Aug 2007 Anabolic Steroids similarity (1)

Deposited unit

A: Hematopoietic prostaglandin D synthase

B: Hematopoietic prostaglandin D synthase

hetero molecules

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

1

Idetical with deposited unit
defined by author&software

Unit cell

Length a, b, c (Å)	47.863, 67.281, 67.204
Angle α, β, γ (deg.)	90.000, 96.830, 90.000
Int Tables number	4
Space group name H-M	P12₁1

#1: Protein	Hematopoietic prostaglandin D synthase / H-PGDS / GST class-sigma / Glutathione S-transferase / Glutathione-dependent PGD synthase / ...H-PGDS / GST class-sigma / Glutathione S-transferase / Glutathione-dependent PGD synthase / Glutathione-requiring prostaglandin D synthase / Prostaglandin-H2 D-isomerase Mass: 23370.830 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: HPGDS, GSTS, PGDS, PTGDS2 / Production host: Escherichia coli (E. coli) References: UniProt: O60760, prostaglandin-D synthase, glutathione transferase
#2: Chemical	ChemComp-GSH / GLUTATHIONE Mass: 307.323 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C₁₀H₁₇N₃O₆S
#3: Chemical	ChemComp-SWS / 7-(azetidin-1-yl)-~{N}-[4-(2-oxidanylpropan-2-yl)cyclohexyl]-1,6-naphthyridine-3-carboxamide Mass: 368.473 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C₂₁H₂₈N₄O₂ / Feature type: SUBJECT OF INVESTIGATION
#4: Water	ChemComp-HOH / water Mass: 18.015 Da / Num. of mol.: 22 / Source method: isolated from a natural source / Formula: H₂O
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: 2.3 Å³/Da / Density % sol: 46.49 %
Crystal grow	Temperature: 295 K / Method: vapor diffusion Details: Protein [10 mg/mL in 50 mM tris(hydroxymethyl)aminomethane hydrochloride at pH 7.5, 50 mM sodium chloride, 1 mM dithiothreitol, 15 mM glutathione, and 1 mM magnesium chloride] was mixed with ...Details: Protein [10 mg/mL in 50 mM tris(hydroxymethyl)aminomethane hydrochloride at pH 7.5, 50 mM sodium chloride, 1 mM dithiothreitol, 15 mM glutathione, and 1 mM magnesium chloride] was mixed with an equal volume of precipitant solution (21% poly(ethylene glycol) 6000, 1% 1,4-dioxane, 5.5% glycerol, 10 mM dithiothreitol, and 60 mM tris(hydroxymethyl)aminomethane hydrochloride at pH 8.5 PH range: 7.5-8.5

Crystal

Density Matthews: 2.3 Å³/Da / Density % sol: 46.49 %

Crystal grow

Temperature: 295 K / Method: vapor diffusion
Details: Protein [10 mg/mL in 50 mM tris(hydroxymethyl)aminomethane hydrochloride at pH 7.5, 50 mM sodium chloride, 1 mM dithiothreitol, 15 mM glutathione, and 1 mM magnesium chloride] was mixed with ...
PH range: 7.5-8.5

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Data collection

Diffraction

Mean temperature: 100 K / Serial crystal experiment: N

Diffraction source

Source:

SYNCHROTRON / Site:

APS

/ Beamline: 21-ID-D / Wavelength: 1.0782 Å

Detector

Type: MARMOSAIC 300 mm CCD / Detector: CCD / Date: Mar 25, 2016

Radiation

Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray

Radiation wavelength

Wavelength: 1.0782 Å / Relative weight: 1

Reflection

Resolution: 2.395→67.281 Å / Num. obs: 15587 / % possible obs: 92.9 % / Redundancy: 3.5 % / CC_1/2: 0.998 / R_merge(I) obs: 0.054 / R_pim(I) all: 0.034 / R_rim(I) all: 0.064 / Net I/σ(I): 13.5

Reflection shell

Diffraction-ID: 1

Resolution (Å)	Redundancy (%)	R_merge(I) obs	Num. measured all	Num. unique obs	CC_1/2	R_pim(I) all	R_rim(I) all	Net I/σ(I) obs	% possible all
2.395-2.403	3.2	0.508	298	93	0.72	0.346	0.619	2.3	60.4
11.099-67.281	2.9	0.033	511	174	0.996	0.023	0.04	26.6	94.6

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Processing

Software

Name	Version	Classification
PHENIX	1.17.1	refinement
Aimless		data scaling
PDB_EXTRACT	3.25	data extraction
DENZO		data reduction
PHENIX		phasing

Refinement

Method to determine structure:

MOLECULAR REPLACEMENT
Starting model: in-house model

Resolution: 2.395→47.38 Å / SU ML: 0.39 / Cross valid method: THROUGHOUT / σ(F): 1.22 / Phase error: 32.47

	R_factor	Num. reflection	% reflection
R_free	0.2478	1465	4.97 %
R_work	0.1847	-	-
obs	0.1879	15587	90.12 %

Solvent computation

Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å

Displacement parameters

B_iso max: 159.83 Å² / B_iso mean: 70 Å² / B_iso min: 34.05 Å²

Refinement step

Cycle: final / Resolution: 2.395→47.38 Å

	Protein	Nucleic acid	Ligand	Solvent	Total
Num. atoms	3067	0	74	22	3163
B_iso mean	-	-	80.78	54.9	-
Num. residues	-	-	-	-	398

LS refinement shell

Refine-ID: X-RAY DIFFRACTION / R_factor R_free error: 0

Resolution (Å)	R_factor R_free	Num. reflection R_free	R_factor R_work	Num. reflection R_work	% reflection obs (%)
2.395-2.48	0.4658	126	0.3509	1894	63
2.48-2.58	0.3448	125	0.3124	2564	81
2.58-2.7	0.3415	181	0.2866	2901	94
2.7-2.84	0.3293	160	0.2528	2976	96
2.84-3.02	0.2803	152	0.2254	2943	95
3.02-3.25	0.286	188	0.2072	3000	96
3.25-3.58	0.2534	149	0.1796	2938	95
3.58-4.09	0.2142	157	0.154	2898	93
4.09-5.16	0.2035	134	0.1372	3015	96
5.16-10	0.1894	93	0.1655	2889	91

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	5.8929	0.5268	1.372	6.1821	1.561	4.7568	-0.1246	0.0996	0.2286	-1.2159	0.3706	-1.3025	-0.2261	0.402	-0.2993	0.5963	-0.0582	0.2079	0.3681	-0.062	0.9301	59.71	-0.7549	63.8853
2	1.939	-0.3572	-0.223	0.0682	0.1579	3.5192	-0.1624	0.8692	0.317	-0.1562	0.1105	-2.6438	-0.2583	1.3633	-0.0567	0.4581	-0.0166	0.0591	0.8437	-0.1388	1.9268	69.1259	6.1032	74.8469
3	3.0242	1.1051	-2.7704	8.8094	-0.4143	2.5932	0.2364	-0.0689	1.1757	-1.3739	-0.4913	-1.4862	-0.8566	0.3535	0.2903	0.6309	0.0181	0.2297	0.531	0.0354	1.227	59.1651	10.3734	67.358
4	2.6458	1.1957	-2.5287	7.0179	-1.4627	7.7337	-0.052	0.0681	0.357	-0.2833	-0.0067	0.7198	-0.0552	-0.4371	0.0828	0.3595	-0.0176	-0.1021	0.3209	-0.0451	0.7406	45.4212	0.0359	72.8216
5	5.4544	3.3307	-3.5637	9.3936	-3.4144	6.6791	0.2868	-0.6689	0.4908	2.1206	0.3572	-1.1596	0.1407	0.842	-0.6216	0.9687	0.288	-0.3836	0.7907	-0.0872	1.3001	62.9396	-13.0806	86.5403
6	2.195	-0.2413	3.3144	5.6757	0.257	8.9045	0.1166	-0.9324	-0.807	0.9714	-0.1374	1.6229	1.0696	-1.1659	-0.0012	0.7736	-0.1815	0.2245	0.6524	0.1694	1.1129	43.6217	-15.1876	81.2291
7	2.3347	2.1586	0.5987	2.0026	0.926	6.3066	0.7845	-0.0293	-1.0426	-0.7428	-0.2864	0.7078	0.7874	-0.3422	-0.3871	0.5102	-0.07	-0.089	0.3692	-0.0241	0.9485	47.0987	-10.8349	70.8808
8	4.9602	3.123	-4.145	7.2628	0.0028	7.4624	-0.2842	-0.24	-0.9394	0.386	-0.0651	-0.1903	1.0631	-0.1841	0.3875	0.6244	-0.023	-0.1876	0.4088	-0.0237	1.2135	47.6684	-20.0541	71.8092
9	6.285	-0.4299	0.814	2.7835	0.8863	5.7134	0.2304	0.6203	-0.3535	-1.2606	-0.1996	-1.3155	0.9073	0.2793	-0.1671	0.7269	0.0315	0.1745	0.3978	-0.1232	1.0975	58.5474	-11.3362	62.0136
10	9.5636	2.6161	-0.223	6.429	2.2253	3.4988	0.4329	-0.6653	0.7201	0.9917	-0.8178	1.2984	0.6402	-0.8844	0.4468	0.6817	-0.0771	0.2921	0.7448	-0.2007	0.8463	37.8028	8.6791	89.6055
11	1.5906	-0.5613	-0.168	9.0113	-0.3723	2.7755	-0.2286	-0.9602	-0.0378	2.1057	0.3933	2.8349	0.5292	-1.334	-0.8417	0.9727	-0.1441	0.5264	1.3721	-0.2821	1.4482	33.0734	7.0058	92.943
12	3.3018	-1.7136	-1.7551	2.5084	-1.2033	3.7163	-0.6597	-0.9159	-0.8848	1.5455	1.4536	1.5124	0.6048	-1.158	-0.2587	1.1545	-0.1873	0.3319	1.0775	0.312	1.2999	39.283	-7.1741	91.4294
13	5.5465	1.7137	-0.3016	3.7738	2.2132	4.6597	-0.0236	0.1107	-0.0599	0.0541	-0.1387	1.1426	0.0483	-0.6595	0.1022	0.3979	0.0516	-0.0173	0.432	-0.0029	0.932	44.3379	8.1116	79.0575
14	4.9516	2.2654	-0.9387	4.6459	1.5676	1.5473	0.7905	-1.0502	-1.6501	1.4559	-0.9821	-0.2434	0.5033	0.8	0.3609	1.2088	-0.0045	-0.353	0.7574	0.2337	0.8738	60.6591	0.7228	97.6785
15	2.4564	1.631	-0.5301	5.2012	-4.3467	3.9938	0.2936	-0.3035	-0.3974	-0.2206	-0.5093	-0.9125	-0.0634	0.7206	0.2356	0.5945	0.0252	-0.1368	0.5017	-0.0904	1.0059	62.9982	15.4806	84.5662
16	6.4505	0.3157	1.7213	6.111	0.3709	9.7595	-0.2665	-0.163	0.6899	0.5266	-0.1431	0.0806	-1.0895	-0.3319	0.3729	0.4962	0.0958	-0.0549	0.3615	-0.1116	0.5516	51.0893	17.5385	85.4833
17	3.4255	1.4416	-0.9335	3.0517	1.5964	3.1962	-0.2104	-1.226	1.2679	1.1607	-0.034	-0.811	-1.0788	0.0002	0.2328	0.8704	0.0464	-0.1839	0.5692	-0.0684	0.7725	56.799	21.7855	91.5005
18	1.2167	0.1289	0.2031	0.7096	-0.5609	0.5337	-0.4321	-0.9914	0.6986	1.5404	0.0574	0.9269	0.1628	-0.9492	-0.4676	0.9545	0.0092	0.5926	0.9798	-0.6787	1.1441	40.5227	17.4336	95.5818

Refinement TLS group

ID	Refine-ID	Refine TLS-ID	Selection details	Auth asym-ID	Auth seq-ID
1	X-RAY DIFFRACTION	1	chain 'A' and (resseq 1:35)	A	1 - 35
2	X-RAY DIFFRACTION	2	chain 'A' and (resseq 36:52)	A	36 - 52
3	X-RAY DIFFRACTION	3	chain 'A' and (resseq 53:63)	A	53 - 63
4	X-RAY DIFFRACTION	4	chain 'A' and (resseq 64:101)	A	64 - 101
5	X-RAY DIFFRACTION	5	chain 'A' and (resseq 102:121)	A	102 - 121
6	X-RAY DIFFRACTION	6	chain 'A' and (resseq 122:135)	A	122 - 135
7	X-RAY DIFFRACTION	7	chain 'A' and (resseq 136:163)	A	136 - 163
8	X-RAY DIFFRACTION	8	chain 'A' and (resseq 164:183)	A	164 - 183
9	X-RAY DIFFRACTION	9	chain 'A' and (resseq 184:199)	A	184 - 199
10	X-RAY DIFFRACTION	10	chain 'B' and (resseq 1:24)	B	1 - 24
11	X-RAY DIFFRACTION	11	chain 'B' and (resseq 25:38)	B	25 - 38
12	X-RAY DIFFRACTION	12	chain 'B' and (resseq 39:52)	B	39 - 52
13	X-RAY DIFFRACTION	13	chain 'B' and (resseq 53:101)	B	53 - 101
14	X-RAY DIFFRACTION	14	chain 'B' and (resseq 102:122)	B	102 - 122
15	X-RAY DIFFRACTION	15	chain 'B' and (resseq 123:135)	B	123 - 135
16	X-RAY DIFFRACTION	16	chain 'B' and (resseq 136:163)	B	136 - 163
17	X-RAY DIFFRACTION	17	chain 'B' and (resseq 164:183)	B	164 - 183
18	X-RAY DIFFRACTION	18	chain 'B' and (resseq 184:199)	B	184 - 199

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