PDB-8uv1: Structure of TDP1 complexed with compound IB01

ID or keywords:

Entry

Database: PDB / ID: 8uv1

Title

Structure of TDP1 complexed with compound IB01

Components

Tyrosyl-DNA phosphodiesterase 1

Keywords

DNA BINDING PROTEIN / phosphodiesterase / drug target / cancer

Function / homology

Function and homology information

3'-tyrosyl-DNA phosphodiesterase activity / Hydrolases; Acting on ester bonds; Phosphoric-diester hydrolases / single strand break repair / exonuclease activity / Nonhomologous End-Joining (NHEJ) / double-strand break repair / single-stranded DNA binding / double-stranded DNA binding / DNA repair / intracellular membrane-bounded organelle ...
Similarity search - Function

Biological species

Homo sapiens (human)

Method

X-RAY DIFFRACTION /

SYNCHROTRON /

MOLECULAR REPLACEMENT / Resolution: 1.83 Å

Authors

Lountos, G.T. / Zhao, X.Z. / Barakat, I. / Wang, W. / Agama, K. / Al Mahmud, M.R. / Pommier, Y. / Burke, T.R.

Funding support

United States, 1items

Citation

Journal: To Be Published
Title: Structure of TDP1 complexed with compound IB01
Authors: Lountos, G.T. / Zhao, X.Z. / Barakat, I. / Wang, W. / Agama, K. / Al Mahmud, M.R. / Pommier, Y. / Burke, T.R.

History

Deposition	Nov 2, 2023	Deposition site: RCSB / Processing site: RCSB
Revision 1.0	Sep 25, 2024	Provider: repository / Type: Initial release
Revision 1.1	Nov 6, 2024	Group: Structure summary / Category: pdbx_entry_details / pdbx_modification_feature / Item: _pdbx_entry_details.has_protein_modification

Structure viewer	Molecule: MolmilJmol/JSmol

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Download

PDBx/mmCIF format	8uv1.cif.gz	383.7 KB	Display	PDBx/mmCIF format
PDB format	pdb8uv1.ent.gz	311.7 KB	Display	PDB format
PDBx/mmJSON format	8uv1.json.gz		Tree view	PDBx/mmJSON format
Others	Other downloads

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Validation report

Summary document	8uv1_validation.pdf.gz	2.4 MB	Display	wwPDB validaton report
Full document	8uv1_full_validation.pdf.gz	2.4 MB	Display
Data in XML	8uv1_validation.xml.gz	45.5 KB	Display
Data in CIF	8uv1_validation.cif.gz	62.6 KB	Display
Arichive directory	https://data.pdbj.org/pub/pdb/validation_reports/uv/8uv1 ftp://data.pdbj.org/pub/pdb/validation_reports/uv/8uv1	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	#234 - Jun 2019 MDM2 and Cancer similarity (1) #55 - Jul 2004 DNA Ligase similarity (1) #241 - Jan 2020 Twenty Years of Molecules similarity (1)

Deposited unit

A: Tyrosyl-DNA phosphodiesterase 1

B: Tyrosyl-DNA phosphodiesterase 1

hetero molecules

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

1

A: Tyrosyl-DNA phosphodiesterase 1

hetero molecules

defined by author&software
53 kDa, 1 polymers
Search similar-shape structures of this assembly by Omokage search (details)

2

B: Tyrosyl-DNA phosphodiesterase 1

hetero molecules

defined by author&software
53.3 kDa, 1 polymers
Search similar-shape structures of this assembly by Omokage search (details)

Unit cell

Length a, b, c (Å)	49.958, 105.022, 193.038
Angle α, β, γ (deg.)	90.00, 90.00, 90.00
Int Tables number	19
Space group name H-M	P2₁2₁2₁

#1: Protein	Tyrosyl-DNA phosphodiesterase 1 / Tyr-DNA phosphodiesterase 1 Mass: 52126.336 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: TDP1 / Plasmid: pDN2454 / Production host: Escherichia coli (E. coli) References: UniProt: Q9NUW8, Hydrolases; Acting on ester bonds; Phosphoric-diester hydrolases
#2: Chemical	ChemComp-XK6 / 8-(fluorosulfonyl)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid Mass: 271.222 Da / Num. of mol.: 7 / Source method: obtained synthetically / Formula: C₁₀H₆FNO₅S / Feature type: SUBJECT OF INVESTIGATION
#3: Chemical	ChemComp-EDO / 1,2-ETHANEDIOL / ETHYLENE GLYCOL Mass: 62.068 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Formula: C₂H₆O₂
#4: Water	ChemComp-HOH / water Mass: 18.015 Da / Num. of mol.: 571 / Source method: isolated from a natural source / Formula: H₂O
Has ligand of interest	Y
Has protein modification	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: 2.43 Å³/Da / Density % sol: 49.36 %
Crystal grow	Temperature: 293 K / Method: vapor diffusion, hanging drop / pH: 7.5 Details: 0.1 M, MOPS/HEPES-NA PH 7.5, 10% (W/V) PEG 8000 20% (V/V) ETHYLENE GLYCOL, 0.03M SODIUM FLUORIDE, 0.03M SODIUM BROMIDE, 0.03M SODIUM IODIDE

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Data collection

Diffraction	Mean temperature: 100 K / Serial crystal experiment: N
Diffraction source	Source: SYNCHROTRON / Site: APS / Beamline: 22-BM / Wavelength: 1 Å
Detector	Type: MARMOSAIC 300 mm CCD / Detector: CCD / Date: Dec 11, 2021
Radiation	Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelength	Wavelength: 1 Å / Relative weight: 1
Reflection	Resolution: 1.83→50 Å / Num. obs: 89424 / % possible obs: 98.8 % / Redundancy: 6.9 % / CC_1/2: 0.995 / R_pim(I) all: 0.034 / R_sym value: 0.084 / Net I/σ(I): 18.5
Reflection shell	Resolution: 1.83→1.86 Å / Redundancy: 6.4 % / Mean I/σ(I) obs: 2.1 / Num. unique obs: 4219 / CC_1/2: 0.865 / CC star: 0.963 / R_pim(I) all: 0.252 / R_sym value: 0.608 / % possible all: 94.4

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Processing

Software

Name	Version	Classification
PHENIX	1.16_3549	refinement
HKL-3000		data reduction
HKL-3000		data scaling
PHASER		phasing

Refinement

Method to determine structure:

MOLECULAR REPLACEMENT / Resolution: 1.83→43.851 Å / SU ML: 0.15 / Cross valid method: FREE R-VALUE / σ(F): 1.38 / Phase error: 18.44 / Stereochemistry target values: ML

	R_factor	Num. reflection	% reflection
R_free	0.1921	4401	4.93 %
R_work	0.1629	-	-
obs	0.1644	89336	98.66 %

Solvent computation

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

Refinement step

Cycle: LAST / Resolution: 1.83→43.851 Å

	Protein	Nucleic acid	Ligand	Solvent	Total
Num. atoms	6970	0	130	571	7671

Refine LS restraints

Refine-ID	Type	Dev ideal	Number
X-RAY DIFFRACTION	f_bond_d	0.006	7598
X-RAY DIFFRACTION	f_angle_d	0.832	10380
X-RAY DIFFRACTION	f_dihedral_angle_d	6.478	6019
X-RAY DIFFRACTION	f_chiral_restr	0.055	1061
X-RAY DIFFRACTION	f_plane_restr	0.006	1316

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 (%)
1.8303-1.8511	0.2583	137	0.2031	2582	X-RAY DIFFRACTION	90
1.8511-1.8729	0.2404	131	0.1958	2652	X-RAY DIFFRACTION	95
1.8729-1.8958	0.2396	113	0.184	2740	X-RAY DIFFRACTION	96
1.8958-1.9198	0.2195	153	0.1793	2730	X-RAY DIFFRACTION	97
1.9198-1.945	0.2245	134	0.1807	2775	X-RAY DIFFRACTION	97
1.945-1.9717	0.2165	119	0.1789	2770	X-RAY DIFFRACTION	98
1.9717-1.9998	0.2139	142	0.1768	2809	X-RAY DIFFRACTION	98
1.9998-2.0297	0.2363	160	0.1718	2721	X-RAY DIFFRACTION	98
2.0297-2.0614	0.2083	144	0.1677	2794	X-RAY DIFFRACTION	98
2.0614-2.0952	0.1917	143	0.1601	2820	X-RAY DIFFRACTION	99
2.0952-2.1313	0.191	130	0.1594	2805	X-RAY DIFFRACTION	99
2.1313-2.1701	0.2127	154	0.1649	2829	X-RAY DIFFRACTION	99
2.1701-2.2118	0.1868	134	0.1575	2802	X-RAY DIFFRACTION	99
2.2118-2.257	0.205	140	0.1609	2847	X-RAY DIFFRACTION	99
2.257-2.306	0.2514	134	0.1635	2826	X-RAY DIFFRACTION	99
2.306-2.3597	0.1928	156	0.1604	2845	X-RAY DIFFRACTION	100
2.3597-2.4187	0.1805	159	0.1656	2844	X-RAY DIFFRACTION	100
2.4187-2.4841	0.195	160	0.1609	2831	X-RAY DIFFRACTION	100
2.4841-2.5572	0.2232	143	0.1725	2852	X-RAY DIFFRACTION	100
2.5572-2.6397	0.2228	154	0.1629	2878	X-RAY DIFFRACTION	100
2.6397-2.734	0.216	141	0.1633	2844	X-RAY DIFFRACTION	100
2.734-2.8435	0.1999	121	0.1698	2909	X-RAY DIFFRACTION	100
2.8435-2.9729	0.2042	162	0.1688	2878	X-RAY DIFFRACTION	100
2.9729-3.1296	0.1928	153	0.1767	2888	X-RAY DIFFRACTION	100
3.1296-3.3256	0.1949	159	0.1656	2901	X-RAY DIFFRACTION	100
3.3256-3.5822	0.1837	165	0.159	2863	X-RAY DIFFRACTION	100
3.5822-3.9425	0.1591	149	0.1486	2894	X-RAY DIFFRACTION	100
3.9425-4.5125	0.1522	170	0.134	2946	X-RAY DIFFRACTION	100
4.5125-5.6833	0.1719	168	0.1453	2946	X-RAY DIFFRACTION	100
5.6833-43.8	0.1824	173	0.1857	3114	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	1.6934	-0.1879	0.3944	0.7235	-0.09	1.7311	-0.0716	-0.1647	0.1004	0.0511	0.0197	0.0796	-0.0995	-0.2438	0.0452	0.1248	0.0175	-0.0076	0.0994	-0.0015	0.1358	1.5598	0.4286	-40.2358
2	1.6398	-0.5053	0.481	1.53	-0.5224	1.7437	0.0985	0.2412	-0.2714	-0.2358	-0.0556	-0.0273	0.3685	0.142	-0.0007	0.2096	-0.002	0.0039	0.1154	-0.0198	0.1728	13.8673	-15.6184	-53.3816
3	1.4545	-0.1072	0.4511	0.3632	-0.0526	1.8254	0.0112	-0.1257	-0.1291	0.0298	0.0005	-0.0378	0.229	0.1577	0.014	0.1436	0.0165	0.0018	0.0934	0.0236	0.1467	20.5219	-13.4418	-37.9226
4	1.7124	0.3774	0.3799	1.0485	-0.4632	1.9299	-0.0279	0.4488	0.1738	-0.079	-0.2149	-0.2508	-0.1566	0.5006	0.124	0.2	-0.0207	0.0061	0.3561	0.164	0.2302	13.6307	11.3875	-89.6523
5	1.5449	-0.0002	0.6233	0.6033	-0.2184	2.5155	0.0123	-0.0291	-0.2403	0.0427	-0.0842	-0.0608	0.3609	0.0858	0.0656	0.1835	0.0337	0.0509	0.1833	0.0694	0.1959	5.2769	-3.117	-81.3096
6	1.1754	0.2062	0.2275	0.4694	-0.3471	2.7969	-0.0316	0.0954	-0.1902	-0.0676	0.0002	-0.0014	0.3932	-0.2784	0.0028	0.1877	-0.0124	0.0325	0.1885	0.016	0.1841	-4.6428	-2.8052	-92.49

Refinement TLS group

ID	Refine-ID	Refine TLS-ID	Selection details
1	X-RAY DIFFRACTION	1	chain 'A' and (resid 162 through 343 )
2	X-RAY DIFFRACTION	2	chain 'A' and (resid 344 through 436 )
3	X-RAY DIFFRACTION	3	chain 'A' and (resid 437 through 607 )
4	X-RAY DIFFRACTION	4	chain 'B' and (resid 162 through 280 )
5	X-RAY DIFFRACTION	5	chain 'B' and (resid 281 through 452 )
6	X-RAY DIFFRACTION	6	chain 'B' and (resid 453 through 607 )

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