PDB-8ptt: Human NUDT5 in complex with MRK-952

ID or keywords:

Entry

Database: PDB / ID: 8ptt

Title

Human NUDT5 in complex with MRK-952

Components

ADP-sugar pyrophosphatase

Keywords

HYDROLASE / Inhibitor

Function / homology

Function and homology information

ADP-D-ribose pyrophosphorylase / ribonucleoside diphosphate catabolic process / nucleobase-containing small molecule metabolic process / 8-oxo-dGDP phosphatase / ADP-sugar diphosphatase activity / ADP-ribose diphosphatase / D-ribose catabolic process / ADP-ribose diphosphatase activity / nucleoside phosphate metabolic process / ribose phosphate metabolic process ...
Similarity search - Function

Biological species

Homo sapiens (human)

Method

X-RAY DIFFRACTION /

SYNCHROTRON /

MOLECULAR REPLACEMENT / Resolution: 2.5 Å

Authors

Diaz-Saez, L. / Koekemoer, L. / Feyerherm, C. / Sloman, S. / Fischer, C. / Schneider, S. / von Delft, F. / Arrowsmith, C.H. / Edwards, A.M. / Bountra, C. / Huber, K.V.M.

Funding support

Canada, 1items

Citation

Journal: To Be Published
Title: Human NUDT5 in complex with MRK-952
Authors: Diaz-Saez, L. / Koekemoer, L. / Feyerherm, C. / Sloman, S. / Fischer, C. / Schneider, S. / von Delft, F. / Arrowsmith, C.H. / Edwards, A.M. / Bountra, C. / Huber, K.V.M.

History

Deposition	Jul 14, 2023	Deposition site: PDBE / Processing site: PDBE
Revision 1.0	Jul 24, 2024	Provider: repository / Type: Initial release

Structure viewer	Molecule: MolmilJmol/JSmol

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Download

PDBx/mmCIF format	8ptt.cif.gz	180.6 KB	Display	PDBx/mmCIF format
PDB format	pdb8ptt.ent.gz		Display	PDB format
PDBx/mmJSON format	8ptt.json.gz		Tree view	PDBx/mmJSON format
Others	Other downloads

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Validation report

Summary document	8ptt_validation.pdf.gz	1.4 MB	Display	wwPDB validaton report
Full document	8ptt_full_validation.pdf.gz	1.4 MB	Display
Data in XML	8ptt_validation.xml.gz	33.3 KB	Display
Data in CIF	8ptt_validation.cif.gz	45.5 KB	Display
Arichive directory	https://data.pdbj.org/pub/pdb/validation_reports/pt/8ptt ftp://data.pdbj.org/pub/pdb/validation_reports/pt/8ptt	HTTPS FTP

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Related structure data

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	#145 - Jan 2012 Messenger RNA Capping similarity (6) #201 - Sep 2016 Isoprene Synthase similarity (4)

Deposited unit

A: ADP-sugar pyrophosphatase

B: ADP-sugar pyrophosphatase

C: ADP-sugar pyrophosphatase

D: ADP-sugar pyrophosphatase

hetero molecules

99.3 kDa, 4 polymers
Search similar-shape structures of this assembly by Omokage search (details)

1

A: ADP-sugar pyrophosphatase

B: ADP-sugar pyrophosphatase

hetero molecules

defined by author
Evidence: gel filtration
49.7 kDa, 2 polymers
Search similar-shape structures of this assembly by Omokage search (details)

2

C: ADP-sugar pyrophosphatase

D: ADP-sugar pyrophosphatase

hetero molecules

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

Unit cell

Length a, b, c (Å)	49.245, 59.679, 81.171
Angle α, β, γ (deg.)	78.789, 81.715, 76.034
Int Tables number	1
Space group name H-M	P1

#1: Protein	ADP-sugar pyrophosphatase / 8-oxo-dGDP phosphatase / Nuclear ATP-synthesis protein NUDIX5 / Nucleoside diphosphate-linked ...8-oxo-dGDP phosphatase / Nuclear ATP-synthesis protein NUDIX5 / Nucleoside diphosphate-linked moiety X motif 5 / hNUDT5 / YSA1H Mass: 24355.596 Da / Num. of mol.: 4 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: NUDT5, NUDIX5, HSPC115 / Production host: Escherichia coli (E. coli) / Strain (production host): BL21 Rosetta 2 (DE3) References: UniProt: Q9UKK9, ADP-ribose diphosphatase, 8-oxo-dGDP phosphatase, ADP-D-ribose pyrophosphorylase
#2: Chemical	ChemComp-F2V / 6-[(5~{R})-7-[3-chloranyl-4-(trifluoromethyl)phenyl]-2,7-diazaspiro[4.4]nonan-2-yl]-7-methyl-purine Mass: 436.861 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: C₂₀H₂₀ClF₃N₆ / Feature type: SUBJECT OF INVESTIGATION
#3: Chemical	ChemComp-MG / MAGNESIUM ION Mass: 24.305 Da / Num. of mol.: 7 / Source method: obtained synthetically / Formula: Mg
#4: Water	ChemComp-HOH / water Mass: 18.015 Da / Num. of mol.: 290 / 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: 2.32 Å³/Da / Density % sol: 46.95 %
Crystal grow	Temperature: 293 K / Method: vapor diffusion, sitting drop / pH: 8 Details: Reservoir: 33% PEG 400, 0.2 M magnesium chloride, and 0.1 M tris pH 8.0

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Data collection

Diffraction	Mean temperature: 100 K / Serial crystal experiment: N
Diffraction source	Source: SYNCHROTRON / Site: Diamond / Beamline: I03 / Wavelength: 0.97628 Å
Detector	Type: DECTRIS EIGER X 16M / Detector: PIXEL / Date: May 12, 2021
Radiation	Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelength	Wavelength: 0.97628 Å / Relative weight: 1
Reflection	Resolution: 2.5→28.41 Å / Num. obs: 29822 / % possible obs: 98.4 % / Redundancy: 3.2 % / B_iso Wilson estimate: 33.048 Å² / R_merge(I) obs: 0.051 / Net I/σ(I): 9.2
Reflection shell	Resolution: 2.5→2.6 Å / Redundancy: 3.5 % / R_merge(I) obs: 0.225 / Mean I/σ(I) obs: 2.9 / Num. unique obs: 3405 / % possible all: 97.9

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Processing

Software

Name	Version	Classification
REFMAC	5.8.0415	refinement
xia2		data reduction
Aimless	0.7.7	data scaling
PHASER	2.8.3	phasing
REFMAC	5.8.0415	refinement

Refinement

Method to determine structure:

MOLECULAR REPLACEMENT / Resolution: 2.5→28.41 Å / Cor.coef. F_o:F_c: 0.956 / Cor.coef. F_o:F_c free: 0.917 / SU B: 10.15 / SU ML: 0.22 / Cross valid method: THROUGHOUT / ESU R: 0.815 / ESU R Free: 0.302

	R_factor	Num. reflection	% reflection
R_free	0.2453	1433	4.805 %
R_work	0.178	28389	-
all	0.181	-	-
obs	-	29822	98.439 %

Solvent computation

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

Displacement parameters

B_iso mean: 39.036 Å²

	B_aniso -1	B_aniso -2	B_aniso -3
1-	2.431 Å²	0.788 Å²	0.886 Å²
2-	-	-0.257 Å²	0.678 Å²
3-	-	-	-1.241 Å²

Refinement step

Cycle: LAST / Resolution: 2.5→28.41 Å

	Protein	Nucleic acid	Ligand	Solvent	Total
Num. atoms	6062	0	127	290	6479

Refine LS restraints

Refine-ID	Type	Dev ideal	Dev ideal target	Number
X-RAY DIFFRACTION	r_bond_refined_d	0.002	0.012	6433
X-RAY DIFFRACTION	r_bond_other_d	0.001	0.016	6084
X-RAY DIFFRACTION	r_angle_refined_deg	1.226	1.67	8786
X-RAY DIFFRACTION	r_angle_other_deg	0.289	1.573	14112
X-RAY DIFFRACTION	r_dihedral_angle_1_deg	6.731	5	808
X-RAY DIFFRACTION	r_dihedral_angle_2_deg	7.804	5.8	50
X-RAY DIFFRACTION	r_dihedral_angle_3_deg	14.43	10	1102
X-RAY DIFFRACTION	r_dihedral_angle_6_deg	12.941	10	280
X-RAY DIFFRACTION	r_chiral_restr	0.232	0.2	987
X-RAY DIFFRACTION	r_gen_planes_refined	0.003	0.02	7511
X-RAY DIFFRACTION	r_gen_planes_other	0.001	0.02	1313
X-RAY DIFFRACTION	r_nbd_refined	0.186	0.2	1047
X-RAY DIFFRACTION	r_symmetry_nbd_other	0.183	0.2	5372
X-RAY DIFFRACTION	r_nbtor_refined	0.166	0.2	2931
X-RAY DIFFRACTION	r_symmetry_nbtor_other	0.082	0.2	3301
X-RAY DIFFRACTION	r_xyhbond_nbd_refined	0.151	0.2	307
X-RAY DIFFRACTION	r_symmetry_xyhbond_nbd_other	0.038	0.2	1
X-RAY DIFFRACTION	r_symmetry_nbd_refined	0.125	0.2	18
X-RAY DIFFRACTION	r_nbd_other	0.165	0.2	50
X-RAY DIFFRACTION	r_symmetry_xyhbond_nbd_refined	0.123	0.2	7
X-RAY DIFFRACTION	r_mcbond_it	1.663	4.037	3169
X-RAY DIFFRACTION	r_mcbond_other	1.662	4.037	3169
X-RAY DIFFRACTION	r_mcangle_it	2.856	7.248	3965
X-RAY DIFFRACTION	r_mcangle_other	2.855	7.248	3966
X-RAY DIFFRACTION	r_scbond_it	1.625	4.24	3264
X-RAY DIFFRACTION	r_scbond_other	1.625	4.24	3265
X-RAY DIFFRACTION	r_scangle_it	2.825	7.696	4810
X-RAY DIFFRACTION	r_scangle_other	2.825	7.696	4811
X-RAY DIFFRACTION	r_lrange_it	4.989	39.27	6746
X-RAY DIFFRACTION	r_lrange_other	4.969	39.297	6711

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 (%)
2.5-2.564	0.308	111	0.244	2087	X-RAY DIFFRACTION	98.4767
2.564-2.634	0.345	109	0.243	2008	X-RAY DIFFRACTION	97.7378
2.634-2.71	0.29	106	0.253	1971	X-RAY DIFFRACTION	97.7872
2.71-2.792	0.348	98	0.227	1912	X-RAY DIFFRACTION	98.6261
2.792-2.883	0.267	82	0.218	1882	X-RAY DIFFRACTION	98.2491
2.883-2.983	0.264	96	0.208	1759	X-RAY DIFFRACTION	97.8892
2.983-3.095	0.296	101	0.211	1774	X-RAY DIFFRACTION	99.1015
3.095-3.219	0.268	81	0.212	1650	X-RAY DIFFRACTION	98.6887
3.219-3.36	0.256	83	0.203	1597	X-RAY DIFFRACTION	98.1882
3.36-3.522	0.248	83	0.183	1578	X-RAY DIFFRACTION	98.4588
3.522-3.709	0.226	64	0.17	1438	X-RAY DIFFRACTION	99.2074
3.709-3.93	0.247	83	0.17	1394	X-RAY DIFFRACTION	98.7299
3.93-4.196	0.187	58	0.137	1310	X-RAY DIFFRACTION	99.1304
4.196-4.524	0.264	51	0.142	1253	X-RAY DIFFRACTION	99.0881
4.524-4.943	0.181	60	0.134	1110	X-RAY DIFFRACTION	99.0686
4.943-5.506	0.23	40	0.144	1023	X-RAY DIFFRACTION	98.4259
5.506-6.318	0.223	34	0.175	908	X-RAY DIFFRACTION	98.5356
6.318-7.644	0.241	43	0.147	749	X-RAY DIFFRACTION	98.0198
7.644-10.44	0.156	29	0.126	609	X-RAY DIFFRACTION	99.0683
10.44-28.41	0.183	21	0.183	377	X-RAY DIFFRACTION	99.005

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