PDB-9da2: Crystal structure of human DNPH1 bound to inhibitor 1b

ID or keywords:

Entry

Database: PDB / ID: 9da2

Title

Crystal structure of human DNPH1 bound to inhibitor 1b

Components

5-hydroxymethyl-dUMP N-hydrolase

Keywords

HYDROLASE/INHIBITOR / Inhibitor / Complex / HYDROLASE / HYDROLASE-INHIBITOR complex

Function / homology

Function and homology information

purine nucleotide catabolic process / deoxyribonucleoside monophosphate catabolic process / 5-hydroxymethyl-dUMP N-hydrolase activity / nucleoside salvage / Purine catabolism / Hydrolases; Glycosylases; Hydrolysing N-glycosyl compounds / epithelial cell differentiation / positive regulation of cell growth / protein homodimerization activity / extracellular exosome ...
Similarity search - Function

Biological species

Homo sapiens (human)

Method

X-RAY DIFFRACTION /

SYNCHROTRON /

MOLECULAR REPLACEMENT / Resolution: 1.13 Å

Authors

Wagner, A.G. / Schramm, V.L. / Almo, S.C. / Ghosh, A.

Funding support

United States, 2items

Organization	Grant number	Country
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)	GM041916	United States
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)	S10 OD020068	United States

Citation

Journal: J.Med.Chem. / Year: 2025
Title: Transition State Analogs of Human DNPH1 Reveal Two Electrophile Migration Mechanisms.
Authors: Wagner, A.G. / Lang, T.B.D. / Ledingham, E.T. / Ghosh, A. / Brooks, D. / Eskandari, R. / Suthagar, K. / Almo, S.C. / Lamiable-Oulaidi, F. / Tyler, P.C. / Schramm, V.L.

History

Deposition	Aug 21, 2024	Deposition site: RCSB / Processing site: RCSB
Revision 1.0	Feb 5, 2025	Provider: repository / Type: Initial release
Revision 1.1	Feb 26, 2025	Group: Database references / Category: citation / citation_author Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _citation_author.identifier_ORCID

Structure viewer	Molecule: MolmilJmol/JSmol

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Download

PDBx/mmCIF format	9da2.cif.gz	168 KB	Display	PDBx/mmCIF format
PDB format	pdb9da2.ent.gz		Display	PDB format
PDBx/mmJSON format	9da2.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/da/9da2 ftp://data.pdbj.org/pub/pdb/validation_reports/da/9da2	HTTPS FTP

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Related structure data

Related structure data	9da1C 9da3C 9da4C 9da5C 9da6C 4p5e 8qhq 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

Deposited unit

A: 5-hydroxymethyl-dUMP N-hydrolase

B: 5-hydroxymethyl-dUMP N-hydrolase

hetero molecules

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

1

Idetical with deposited unit
defined by author&software
Evidence: gel filtration, Superdes S200

Unit cell

Length a, b, c (Å)	60.538, 64.768, 128.758
Angle α, β, γ (deg.)	90.00, 90.00, 90.00
Int Tables number	20
Space group name H-M	C222₁

Components on special symmetry positions

ID	Model	Components
1	1	A-359- HOH
2	1	A-393- HOH
3	1	B-342- HOH
4	1	B-386- HOH

#1: Protein	5-hydroxymethyl-dUMP N-hydrolase / 2'-deoxynucleoside 5'-phosphate N-hydrolase 1 / c-Myc-responsive protein RCL Mass: 16224.247 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: DNPH1, C6orf108, RCL / Plasmid: pET-28a(+) / Details (production host): LIC / Production host: Escherichia coli BL21(DE3) (bacteria) / Variant (production host): pRIL References: UniProt: O43598, Hydrolases; Glycosylases; Hydrolysing N-glycosyl compounds
#2: Chemical	ChemComp-A1BBC / 1-(2-deoxy-2-fluoro-5-O-phosphono-beta-D-arabinofuranosyl)-5-(hydroxymethyl)pyrimidine-2,4(1H,3H)-dione Mass: 356.198 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C₁₀H₁₄FN₂O₉P / Feature type: SUBJECT OF INVESTIGATION
#3: Chemical	ChemComp-EDO / 1,2-ETHANEDIOL / ETHYLENE GLYCOL Mass: 62.068 Da / Num. of mol.: 7 / Source method: obtained synthetically / Formula: C₂H₆O₂
#4: Chemical	ChemComp-PEG / DI(HYDROXYETHYL)ETHER Mass: 106.120 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C₄H₁₀O₃
#5: Water	ChemComp-HOH / water Mass: 18.015 Da / Num. of mol.: 219 / Source method: isolated from a natural source / Formula: H₂O
Has ligand of interest	Y
Has protein modification	N

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Experiment

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

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Sample preparation

Crystal	Density Matthews: 1.94 Å³/Da / Density % sol: 36.75 %
Crystal grow	Temperature: 292 K / Method: vapor diffusion, sitting drop / pH: 6 / Details: 20% (w/v) PEG 3350 and 0.2 M Magnesium sulfate

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Data collection

Diffraction	Mean temperature: 100 K / Serial crystal experiment: N
Diffraction source	Source: SYNCHROTRON / Site: NSLS-II / Beamline: 17-ID-1 / Wavelength: 0.92 Å
Detector	Type: DECTRIS EIGER X 9M / Detector: PIXEL / Date: Dec 13, 2023
Radiation	Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelength	Wavelength: 0.92 Å / Relative weight: 1
Reflection	Resolution: 1.13→29.47 Å / Num. obs: 94224 / % possible obs: 99.8 % / Redundancy: 7.1 % / CC_1/2: 0.997 / R_merge(I) obs: 0.062 / R_pim(I) all: 0.024 / R_rim(I) all: 0.067 / Χ²: 0.96 / Net I/σ(I): 14.5 / Num. measured all: 671663
Reflection shell	Resolution: 1.13→1.15 Å / % possible obs: 97.4 % / Redundancy: 4.4 % / R_merge(I) obs: 0.653 / Num. measured all: 19562 / Num. unique obs: 4483 / CC_1/2: 0.794 / R_pim(I) all: 0.344 / R_rim(I) all: 0.741 / Χ²: 0.91 / Net I/σ(I) obs: 1.9

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Processing

Software

Name	Version	Classification
PHENIX	1.2	refinement
Aimless		data scaling
PHASER		phasing

Refinement

Method to determine structure:

MOLECULAR REPLACEMENT / Resolution: 1.13→29.47 Å / SU ML: 0.1 / Cross valid method: FREE R-VALUE / σ(F): 1.34 / Phase error: 18.14 / Stereochemistry target values: ML

	R_factor	Num. reflection	% reflection
R_free	0.1843	4797	5.09 %
R_work	0.1661	-	-
obs	0.167	94152	99.73 %

Solvent computation

Shrinkage radii: 0.9 Å / VDW probe radii: 1.1 Å / Solvent model: FLAT BULK SOLVENT MODEL

Refinement step

Cycle: LAST / Resolution: 1.13→29.47 Å

	Protein	Nucleic acid	Ligand	Solvent	Total
Num. atoms	1976	0	81	219	2276

Refine LS restraints

Refine-ID	Type	Dev ideal	Number
X-RAY DIFFRACTION	f_bond_d	0.009
X-RAY DIFFRACTION	f_angle_d	1.386
X-RAY DIFFRACTION	f_dihedral_angle_d	8.92	308
X-RAY DIFFRACTION	f_chiral_restr	0.078	302
X-RAY DIFFRACTION	f_plane_restr	0.017	365

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 (%)
1.13-1.14	0.2553	148	0.2581	2853	X-RAY DIFFRACTION	96
1.14-1.16	0.2595	155	0.2381	2909	X-RAY DIFFRACTION	99
1.16-1.17	0.2411	171	0.2248	2933	X-RAY DIFFRACTION	99
1.17-1.19	0.2351	161	0.2259	2900	X-RAY DIFFRACTION	100
1.19-1.2	0.2059	170	0.2191	2980	X-RAY DIFFRACTION	100
1.2-1.22	0.2383	155	0.2124	2916	X-RAY DIFFRACTION	100
1.22-1.24	0.2213	170	0.2077	2978	X-RAY DIFFRACTION	100
1.24-1.25	0.1936	181	0.2044	2905	X-RAY DIFFRACTION	100
1.25-1.27	0.1917	151	0.194	2993	X-RAY DIFFRACTION	100
1.27-1.29	0.1961	147	0.19	2970	X-RAY DIFFRACTION	100
1.29-1.32	0.187	151	0.1881	2969	X-RAY DIFFRACTION	100
1.32-1.34	0.163	157	0.1761	2988	X-RAY DIFFRACTION	100
1.34-1.37	0.1803	142	0.1732	2928	X-RAY DIFFRACTION	100
1.37-1.39	0.1998	131	0.1745	3040	X-RAY DIFFRACTION	100
1.39-1.42	0.1687	164	0.1759	2949	X-RAY DIFFRACTION	100
1.42-1.46	0.1764	162	0.1744	2978	X-RAY DIFFRACTION	100
1.46-1.49	0.1725	153	0.1745	2975	X-RAY DIFFRACTION	100
1.49-1.53	0.1946	158	0.1627	2993	X-RAY DIFFRACTION	100
1.54-1.58	0.1687	136	0.1587	3020	X-RAY DIFFRACTION	100
1.58-1.63	0.1697	156	0.1552	2956	X-RAY DIFFRACTION	100
1.63-1.69	0.1607	147	0.1572	2982	X-RAY DIFFRACTION	100
1.69-1.76	0.1755	157	0.158	3005	X-RAY DIFFRACTION	100
1.76-1.84	0.1602	185	0.1582	2974	X-RAY DIFFRACTION	100
1.84-1.93	0.195	157	0.1587	3006	X-RAY DIFFRACTION	100
1.93-2.05	0.1864	164	0.1558	2977	X-RAY DIFFRACTION	100
2.06-2.21	0.1731	160	0.1507	3048	X-RAY DIFFRACTION	100
2.21-2.44	0.1674	151	0.1562	3014	X-RAY DIFFRACTION	100
2.44-2.79	0.1747	177	0.1594	3029	X-RAY DIFFRACTION	100
2.79-3.51	0.1931	208	0.1595	3009	X-RAY DIFFRACTION	100
3.51-29.47	0.1872	172	0.1665	3178	X-RAY DIFFRACTION	100

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	4.1976	0.6194	2.7373	4.6948	0.2063	3.3753	0.0705	-0.126	-0.7469	0.3945	0.0868	0.1151	1.015	-0.1433	-0.2753	0.3234	-0.0277	0.0212	0.1943	-0.0758	0.3965	-25.9766	-41.6904	-18.1169
2	1.1061	0.5862	0.7736	3.5098	0.1833	2.0215	-0.07	-0.0004	0.0668	0.0986	0.0474	0.1646	-0.2626	-0.016	0.0013	0.1398	0.0023	0.0151	0.1227	-0.0138	0.0975	-20.8031	-5.3668	-6.4049
3	9.1795	6.5753	3.2831	9.6958	2.9473	3.5862	-0.1779	-0.4355	0.0345	0.0089	-0.3865	0.3557	0.1282	-0.1183	0.5785	0.2915	0.0305	0.0294	0.2427	-0.0031	0.1808	-28.5669	-1.0606	-10.0398
4	3.2058	-0.1556	0.4269	3.8282	-0.6137	2.2034	-0.0779	0.1432	-0.1448	-0.0107	0.122	0.6588	-0.0415	-0.294	-0.0549	0.1341	0.0256	0.0217	0.149	-0.027	0.1783	-30.9407	-10.7707	-14.0323
5	2.8399	0.2435	0.9609	3.4965	-0.2981	2.8608	-0.0391	0.1677	0.0804	-0.3194	0.072	0.0796	-0.2018	-0.0507	-0.0297	0.1262	0.0031	0.0127	0.1146	-0.0129	0.0657	-21.0026	-11.5135	-18.0192
6	2.8146	0.6739	0.455	4.1687	1.0809	3.5618	-0.0588	0.113	0.0876	-0.428	0.0676	-0.338	-0.2709	0.1404	0.0032	0.1475	-0.0431	0.0607	0.1677	-0.0129	0.1403	-10.6593	-9.3526	-18.1424
7	5.6692	-1.1142	2.6607	5.3597	-4.4936	8.0983	-0.0704	0.1859	0.3613	-0.3886	0.1738	-0.5064	-0.6085	0.602	0.0345	0.3289	-0.079	0.079	0.1436	-0.0306	0.1718	-13.0737	3.5262	-12.1798
8	5.3351	3.6934	5.4957	5.1168	4.4168	8.3829	-0.1849	0.5006	-0.548	-0.6474	0.1659	0.1362	-0.4114	0.3436	-0.0146	0.2096	0.0053	0.0048	0.2174	-0.1009	0.2309	-20.7198	-31.3329	-26.599
9	1.8631	0.8147	0.8788	7.6237	-1.4195	0.962	-0.029	0.029	-0.3026	0.0244	-0.0238	-0.4155	0.0603	0.1626	0.0707	0.1122	0.0136	0.0201	0.1818	-0.0165	0.1802	-10.2965	-26.9911	-14.6836
10	3.4765	2.7764	4.7928	5.6766	3.9391	8.0609	0.1786	0.3601	-0.5889	-0.1541	-0.1646	-0.0103	0.6551	0.1218	0.0143	0.2466	0.0418	0.0695	0.1887	-0.0925	0.367	-15.4336	-39.0266	-20.7833
11	3.4091	1.6073	-2.4467	2.2265	-2.4079	4.3979	-0.335	0.1737	-0.3371	-0.6141	-0.2492	-0.8083	0.5487	0.0353	0.4925	0.301	0.0295	0.0539	0.3279	-0.1076	0.4881	-18.7557	-34.5183	-30.3906
12	6.5814	2.1472	0.418	2.9462	-0.6481	1.7367	0.2232	1.0121	-0.1612	-0.6446	0.1585	-0.2233	-0.2235	0.3267	-0.3215	0.3562	0.01	0.0637	0.3355	-0.0573	0.1481	-14.7643	-19.6207	-30.6314
13	1.8176	0.1592	0.1525	2.6355	0.3089	1.6694	-0.0064	0.2784	-0.1668	-0.2956	0.0033	0.1056	-0.0962	0.0501	0.0072	0.1109	0.0016	-0.006	0.1451	-0.0356	0.1073	-21.7594	-24.5391	-21.0125
14	1.9963	-0.5716	1.565	3.7426	-2.3502	7.7377	-0.0431	0.2288	-0.2359	-0.3926	0.0132	0.2705	-0.0801	-0.2496	0.0045	0.1302	-0.0113	-0.0323	0.1595	-0.0482	0.1679	-27.5722	-28.0371	-21.9364
15	2.2276	-1.7437	0.9135	4.4427	-1.9819	3.6275	-0.0485	-0.0646	-0.1145	0.1179	-0.0409	0.0759	0.0114	0.0016	0.0715	0.0936	-0.0139	0.0105	0.122	0.0029	0.1522	-23.9945	-26.9628	-7.5998
16	4.9055	0.2605	-0.8799	3.6584	2.2772	2.2086	0.0372	0.1131	-0.2653	-0.1114	-0.1125	0.3953	0.0422	-0.3363	0.0166	0.1	-0.0356	-0.0067	0.1348	-0.0317	0.209	-30.8577	-31.9785	-15.6517

Refinement TLS group

ID	Refine-ID	Refine TLS-ID	Selection details
1	X-RAY DIFFRACTION	1	chain 'B' and (resid 147 through 159 )
2	X-RAY DIFFRACTION	2	chain 'A' and (resid 20 through 48 )
3	X-RAY DIFFRACTION	3	chain 'A' and (resid 49 through 71 )
4	X-RAY DIFFRACTION	4	chain 'A' and (resid 72 through 93 )
5	X-RAY DIFFRACTION	5	chain 'A' and (resid 94 through 119 )
6	X-RAY DIFFRACTION	6	chain 'A' and (resid 120 through 146 )
7	X-RAY DIFFRACTION	7	chain 'A' and (resid 147 through 159 )
8	X-RAY DIFFRACTION	8	chain 'B' and (resid 21 through 26 )
9	X-RAY DIFFRACTION	9	chain 'B' and (resid 27 through 35 )
10	X-RAY DIFFRACTION	10	chain 'B' and (resid 36 through 48 )
11	X-RAY DIFFRACTION	11	chain 'B' and (resid 49 through 71 )
12	X-RAY DIFFRACTION	12	chain 'B' and (resid 72 through 85 )
13	X-RAY DIFFRACTION	13	chain 'B' and (resid 86 through 110 )
14	X-RAY DIFFRACTION	14	chain 'B' and (resid 111 through 119 )
15	X-RAY DIFFRACTION	15	chain 'B' and (resid 120 through 134 )
16	X-RAY DIFFRACTION	16	chain 'B' and (resid 135 through 146 )

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