[English] 日本語
Yorodumi
- PDB-8cw2: Crystal structure of TDP1 complexed with compound XZ760 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 8cw2
TitleCrystal structure of TDP1 complexed with compound XZ760
ComponentsTyrosyl-DNA phosphodiesterase 1
KeywordsHYDROLASE / phosphodiesterase / DNA BINDING PROTEIN
Function / homology
Function and homology information


3'-tyrosyl-DNA phosphodiesterase activity / single strand break repair / Hydrolases; Acting on ester bonds; Phosphoric-diester hydrolases / exonuclease activity / Nonhomologous End-Joining (NHEJ) / double-strand break repair / single-stranded DNA binding / double-stranded DNA binding / intracellular membrane-bounded organelle / DNA repair ...3'-tyrosyl-DNA phosphodiesterase activity / single strand break repair / Hydrolases; Acting on ester bonds; Phosphoric-diester hydrolases / exonuclease activity / Nonhomologous End-Joining (NHEJ) / double-strand break repair / single-stranded DNA binding / double-stranded DNA binding / intracellular membrane-bounded organelle / DNA repair / nucleoplasm / nucleus / plasma membrane / cytoplasm
Similarity search - Function
Tyrosyl-DNA phosphodiesterase I / Tyrosyl-DNA phosphodiesterase
Similarity search - Domain/homology
Chem-OYR / Tyrosyl-DNA phosphodiesterase 1
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.811 Å
AuthorsLountos, G.T. / Zhao, X.Z. / Wang, W. / Kiselev, E. / Tropea, J.E. / Needle, D. / Pommier, Y. / Burke, T.R.
Funding support United States, 1items
OrganizationGrant numberCountry
National Institutes of Health/National Cancer Institute (NIH/NCI) United States
CitationJournal: Rsc Chem Biol / Year: 2023
Title: Identification of multidentate tyrosyl-DNA phosphodiesterase 1 (TDP1) inhibitors that simultaneously access the DNA, protein and catalytic-binding sites by oxime diversification.
Authors: Zhao, X.Z. / Wang, W. / Lountos, G.T. / Kiselev, E. / Tropea, J.E. / Needle, D. / Pommier, Y. / Burke Jr., T.R.
History
DepositionMay 18, 2022Deposition site: RCSB / Processing site: RCSB
Revision 1.0Apr 12, 2023Provider: repository / Type: Initial release
Revision 1.1May 31, 2023Group: Database references / Category: citation / citation_author
Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _citation_author.identifier_ORCID / _citation_author.name
Revision 1.2Oct 25, 2023Group: Data collection / Refinement description
Category: chem_comp_atom / chem_comp_bond / pdbx_initial_refinement_model

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Tyrosyl-DNA phosphodiesterase 1
B: Tyrosyl-DNA phosphodiesterase 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)106,17211
Polymers104,2532
Non-polymers1,9199
Water12,592699
1
A: Tyrosyl-DNA phosphodiesterase 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)53,3238
Polymers52,1261
Non-polymers1,1967
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
2
B: Tyrosyl-DNA phosphodiesterase 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)52,8493
Polymers52,1261
Non-polymers7232
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)49.728, 104.758, 193.213
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number19
Space group name H-MP212121

-
Components

-
Protein , 1 types, 2 molecules AB

#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 / Production host: Escherichia coli (E. coli)
References: UniProt: Q9NUW8, Hydrolases; Acting on ester bonds; Phosphoric-diester hydrolases

-
Non-polymers , 5 types, 708 molecules

#2: Chemical ChemComp-OYR / 4-({(4R)-7-phenyl-2-[4-(2-{[4-(pyridin-2-yl)phenyl]methoxy}ethyl)phenyl]imidazo[1,2-a]pyridin-3-yl}amino)benzene-1,2-dicarboxylic acid


Mass: 660.717 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C41H32N4O5 / Feature type: SUBJECT OF INVESTIGATION
#3: Chemical ChemComp-DMS / DIMETHYL SULFOXIDE


Mass: 78.133 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C2H6OS / Comment: DMSO, precipitant*YM
#4: Chemical ChemComp-MPO / 3[N-MORPHOLINO]PROPANE SULFONIC ACID


Mass: 209.263 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C7H15NO4S / Comment: pH buffer*YM
#5: Chemical
ChemComp-EDO / 1,2-ETHANEDIOL / ETHYLENE GLYCOL


Mass: 62.068 Da / Num. of mol.: 5 / Source method: isolated from a natural source / Formula: C2H6O2
#6: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 699 / Source method: isolated from a natural source / Formula: H2O

-
Details

Has ligand of interestY

-
Experimental details

-
Experiment

ExperimentMethod: X-RAY DIFFRACTION / Number of used crystals: 1

-
Sample preparation

CrystalDensity Matthews: 2.41 Å3/Da / Density % sol: 49.04 %
Crystal growTemperature: 291 K / Method: vapor diffusion, hanging drop
Details: 0.1 M MOPS/HEPES-Na pH 7.5, 10% (w/v) PEG 8000, 20% (v/v) ethylene glycol, 0.03 M sodium fluoride, 0.03 M sodium bromide and 0.03 M sodium iodide

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 22-BM / Wavelength: 1 Å
DetectorType: RAYONIX MX-300 / Detector: CCD / Date: Dec 17, 2021
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 1.81→50 Å / Num. obs: 89034 / % possible obs: 95.9 % / Redundancy: 6.7 % / CC1/2: 0.997 / Rmerge(I) obs: 0.075 / Rpim(I) all: 0.031 / Net I/σ(I): 21.9
Reflection shellResolution: 1.81→1.84 Å / Rmerge(I) obs: 0.692 / Mean I/σ(I) obs: 2.1 / Num. unique obs: 4242 / CC1/2: 0.961 / Rpim(I) all: 0.28

-
Processing

Software
NameVersionClassification
PHENIX1.16_3549refinement
PDB_EXTRACT3.27data extraction
HKL-3000data reduction
HKL-3000data scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 6DHU

6dhu


Resolution: 1.811→40.636 Å / SU ML: 0.16 / Cross valid method: THROUGHOUT / σ(F): 1.35 / Phase error: 18.34 / Stereochemistry target values: ML
RfactorNum. reflection% reflection
Rfree0.1914 4399 4.95 %
Rwork0.1561 84544 -
obs0.1579 88943 95.74 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso max: 105.78 Å2 / Biso mean: 30.196 Å2 / Biso min: 10.64 Å2
Refinement stepCycle: final / Resolution: 1.811→40.636 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms7009 0 122 699 7830
Biso mean--38.57 40.31 -
Num. residues----875
LS refinement shell

Refine-ID: X-RAY DIFFRACTION / Rfactor Rfree error: 0

Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection Rwork% reflection obs (%)
1.811-1.83150.26281310.2291259188
1.8315-1.8530.24431160.2101267092
1.853-1.87560.25261400.1989266291
1.8756-1.89940.24271370.1915270193
1.8994-1.92430.2371330.1821267493
1.9243-1.95070.2221530.1875264892
1.9507-1.97860.23061240.1757274893
1.9786-2.00810.21931270.1738268292
2.0081-2.03950.21531610.1741267493
2.0395-2.07290.19471410.1615276493
2.0729-2.10870.18161310.1482266993
2.1087-2.1470.20081420.1526276094
2.147-2.18830.1861500.1481271894
2.1883-2.2330.1671300.1472275295
2.233-2.28150.20721370.1551277395
2.2815-2.33460.17841420.1494278295
2.3346-2.3930.2011530.1546284897
2.393-2.45760.19911750.1592280497
2.4576-2.530.22471520.1571285498
2.53-2.61160.16521590.162288298
2.6116-2.70490.20491610.1629287999
2.7049-2.81320.22061450.1648293699
2.8132-2.94120.20861510.16042955100
2.9412-3.09620.21321540.16252947100
3.0962-3.29010.19241620.15792959100
3.2901-3.5440.18741750.14792952100
3.544-3.90040.18231430.14112992100
3.9004-4.46420.14521470.12513022100
4.4642-5.62210.15351670.13743040100
5.6221-40.60.19711600.17753206100
Refinement TLS params.

Method: refined / Refine-ID: X-RAY DIFFRACTION

IDL11 (°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)
12.1055-0.37970.08081.0447-0.46811.5448-0.0771-0.10690.46120.0523-0.0376-0.1495-0.26420.03960.09470.18930.0065-0.02480.0893-0.00030.184411.28236.2786-36.9689
21.97490.0921-0.01061.7835-0.3252.0906-0.0737-0.2637-0.00090.10730.11150.22910.0164-0.2894-0.02280.12220.023-0.00190.16850.01940.1477-3.4719-3.1576-35.2745
31.63330.030.44260.6419-0.09892.5907-0.04720.0620.0969-0.05570.03810.1288-0.1-0.24960.00320.1160.0133-0.01780.08680.01280.14970.8312-0.3375-48.3656
41.8403-0.5235-0.14791.1605-0.57742.06710.02020.2484-0.1973-0.23770.01540.07270.3093-0.1087-0.04730.1755-0.0336-0.03780.1398-0.00470.14346.2226-11.9271-55.8092
53.12030.6995-0.30483.2576-1.30861.6743-0.03310.3869-0.3317-0.4118-0.0242-0.15110.53730.26020.04380.22860.040.0060.1753-0.03510.224420.9675-20.3605-51.5075
61.0027-0.04660.4090.29020.01031.23610.0366-0.0764-0.16180.0336-0.0221-0.00410.23250.0598-0.00520.1475-0.0001-0.00480.09090.01670.150117.9298-15.2497-40.242
73.0267-0.08060.37341.27740.02386.70670.1119-0.00810.44930.1766-0.0037-0.157-0.84830.9870.17220.2286-0.0722-0.00690.27880.06440.270226.43551.3183-48.8838
81.53550.01250.53371.26810.23964.16220.0945-0.3031-0.25370.2174-0.0894-0.06160.4689-0.07730.00560.187-0.0073-0.01490.18380.06220.19422.7427-17.159-25.512
92.40570.17650.37641.1749-0.26742.7501-0.01240.34240.2109-0.1025-0.1083-0.1841-0.27230.43220.05340.1997-0.05210.00190.26770.09530.183213.771211.3423-89.5295
101.6521-0.31040.74231.1147-0.56022.365-0.05220.03710.06410.0755-0.0872-0.196-0.05990.40830.140.1395-0.01470.00080.25460.06020.169914.58645.9655-78.2308
111.36410.24910.74331.22970.0142.80790.1605-0.1437-0.34120.0471-0.050.01220.6395-0.1652-0.08660.2543-0.00350.00750.21110.06750.23272.3901-10.2029-80.3848
122.1161-0.00070.2761.6642-0.07783.3764-0.0304-0.0911-0.2579-0.10440.03880.0030.6203-0.6283-0.12130.1715-0.05650.0020.31120.01390.204-8.108-4.8957-92.1057
131.27080.06830.27870.4353-0.19862.67460.02480.0656-0.2085-0.0779-0.0119-0.03380.3949-0.1242-0.0130.2007-0.00640.00810.2020.01990.1841-1.2966-5.5057-90.0613
140.95340.236-0.51620.5843-1.22325.7067-0.00030.0086-0.0318-0.04540.01480.039-0.0119-0.4361-0.0040.12080.0063-0.00340.32050.00690.1984-8.30172.0528-96.2605
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection detailsAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1chain 'A' and (resid 162 through 202 )A162 - 202
2X-RAY DIFFRACTION2chain 'A' and (resid 203 through 280 )A203 - 280
3X-RAY DIFFRACTION3chain 'A' and (resid 281 through 344 )A281 - 344
4X-RAY DIFFRACTION4chain 'A' and (resid 345 through 382 )A345 - 382
5X-RAY DIFFRACTION5chain 'A' and (resid 383 through 436 )A383 - 436
6X-RAY DIFFRACTION6chain 'A' and (resid 437 through 548 )A437 - 548
7X-RAY DIFFRACTION7chain 'A' and (resid 549 through 572 )A549 - 572
8X-RAY DIFFRACTION8chain 'A' and (resid 573 through 607 )A573 - 607
9X-RAY DIFFRACTION9chain 'B' and (resid 162 through 280 )B162 - 280
10X-RAY DIFFRACTION10chain 'B' and (resid 281 through 344 )B281 - 344
11X-RAY DIFFRACTION11chain 'B' and (resid 345 through 421 )B345 - 421
12X-RAY DIFFRACTION12chain 'B' and (resid 422 through 452 )B422 - 452
13X-RAY DIFFRACTION13chain 'B' and (resid 453 through 548 )B453 - 548
14X-RAY DIFFRACTION14chain 'B' and (resid 549 through 608 )B549 - 608

+
About Yorodumi

-
News

-
Feb 9, 2022. New format data for meta-information of EMDB entries

New format data for meta-information of EMDB entries

  • Version 3 of the EMDB header file is now the official format.
  • The previous official version 1.9 will be removed from the archive.

Related info.:EMDB header

External links:wwPDB to switch to version 3 of the EMDB data model

-
Aug 12, 2020. Covid-19 info

Covid-19 info

URL: https://pdbjlvh1.pdbj.org/emnavi/covid19.php

New page: Covid-19 featured information page in EM Navigator.

Related info.:Covid-19 info / Mar 5, 2020. Novel coronavirus structure data

+
Mar 5, 2020. Novel coronavirus structure data

Novel coronavirus structure data

Related info.:Yorodumi Speices / Aug 12, 2020. Covid-19 info

External links:COVID-19 featured content - PDBj / Molecule of the Month (242)：Coronavirus Proteases

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

EMDB accession codes are about to change! (news from PDBe EMDB page)

  • The allocation of 4 digits for EMDB accession codes will soon come to an end. Whilst these codes will remain in use, new EMDB accession codes will include an additional digit and will expand incrementally as the available range of codes is exhausted. The current 4-digit format prefixed with “EMD-” (i.e. EMD-XXXX) will advance to a 5-digit format (i.e. EMD-XXXXX), and so on. It is currently estimated that the 4-digit codes will be depleted around Spring 2019, at which point the 5-digit format will come into force.
  • The EM Navigator/Yorodumi systems omit the EMD- prefix.

Related info.:Q: What is EMD? / ID/Accession-code notation in Yorodumi/EM Navigator

External links:EMDB Accession Codes are Changing Soon! / Contact to PDBj

+
Jul 12, 2017. Major update of PDB

Major update of PDB

  • wwPDB released updated PDB data conforming to the new PDBx/mmCIF dictionary.
  • This is a major update changing the version number from 4 to 5, and with Remediation, in which all the entries are updated.
  • In this update, many items about electron microscopy experimental information are reorganized (e.g. em_software).
  • Now, EM Navigator and Yorodumi are based on the updated data.

External links:wwPDB Remediation / Enriched Model Files Conforming to OneDep Data Standards Now Available in the PDB FTP Archive

-
Yorodumi

Thousand views of thousand structures

  • Yorodumi is a browser for structure data from EMDB, PDB, SASBDB, etc.
  • This page is also the successor to EM Navigator detail page, and also detail information page/front-end page for Omokage search.
  • The word "yorodu" (or yorozu) is an old Japanese word meaning "ten thousand". "mi" (miru) is to see.

Related info.:EMDB / PDB / SASBDB / Comparison of 3 databanks / Yorodumi Search / Aug 31, 2016. New EM Navigator & Yorodumi / Yorodumi Papers / Jmol/JSmol / Function and homology information / Changes in new EM Navigator and Yorodumi

Read more