[English] 日本語
Yorodumi
- PDB-7aop: Structure of NUDT15 in complex with inhibitor TH8321 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 7aop
TitleStructure of NUDT15 in complex with inhibitor TH8321
ComponentsNucleotide triphosphate diphosphatase NUDT15
KeywordsHYDROLASE / NUDIX hydrolase / inhibitor
Function / homology
Function and homology information


nucleoside phosphate catabolic process / purine nucleotide catabolic process / nucleotide diphosphatase / nucleobase-containing small molecule metabolic process / nucleoside triphosphate diphosphatase activity / 8-oxo-dGDP phosphatase activity / dGTP catabolic process / 8-oxo-7,8-dihydrodeoxyguanosine triphosphate pyrophosphatase activity / 8-oxo-7,8-dihydroguanosine triphosphate pyrophosphatase activity / DNA protection ...nucleoside phosphate catabolic process / purine nucleotide catabolic process / nucleotide diphosphatase / nucleobase-containing small molecule metabolic process / nucleoside triphosphate diphosphatase activity / 8-oxo-dGDP phosphatase activity / dGTP catabolic process / 8-oxo-7,8-dihydrodeoxyguanosine triphosphate pyrophosphatase activity / 8-oxo-7,8-dihydroguanosine triphosphate pyrophosphatase activity / DNA protection / Phosphate bond hydrolysis by NUDT proteins / Azathioprine ADME / xenobiotic catabolic process / regulation of proteasomal protein catabolic process / response to reactive oxygen species / mitotic cell cycle / metal ion binding / cytosol
Similarity search - Function
NUDIX domain / Nudix hydrolase domain profile. / NUDIX hydrolase domain / NUDIX hydrolase-like domain superfamily
Similarity search - Domain/homology
Chem-RTW / Nucleotide triphosphate diphosphatase NUDT15
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.35 Å
AuthorsRehling, D. / Zhang, S.M. / Helleday, T. / Stenmark, P.
Funding support Sweden, 1items
OrganizationGrant numberCountry
Swedish Research Council Sweden
CitationJournal: Cell Chem Biol / Year: 2021
Title: NUDT15-mediated hydrolysis limits the efficacy of anti-HCMV drug ganciclovir.
Authors: Zhang, S.M. / Rehling, D. / Jemth, A.S. / Throup, A. / Landazuri, N. / Almlof, I. / Gottmann, M. / Valerie, N.C.K. / Borhade, S.R. / Wakchaure, P. / Page, B.D.G. / Desroses, M. / Homan, E.J. ...Authors: Zhang, S.M. / Rehling, D. / Jemth, A.S. / Throup, A. / Landazuri, N. / Almlof, I. / Gottmann, M. / Valerie, N.C.K. / Borhade, S.R. / Wakchaure, P. / Page, B.D.G. / Desroses, M. / Homan, E.J. / Scobie, M. / Rudd, S.G. / Berglund, U.W. / Soderberg-Naucler, C. / Stenmark, P. / Helleday, T.
History
DepositionOct 14, 2020Deposition site: PDBE / Processing site: PDBE
Revision 1.0Jun 2, 2021Provider: repository / Type: Initial release
Revision 1.1Jul 14, 2021Group: Database references / Category: citation / citation_author
Item: _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed ..._citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _citation_author.name
Revision 1.2Dec 29, 2021Group: Database references / Category: citation / database_2
Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _database_2.pdbx_DOI / _database_2.pdbx_database_accession
Revision 1.3Dec 21, 2022Group: Database references / Source and taxonomy / Structure summary
Category: citation / entity ...citation / entity / entity_name_com / entity_src_gen
Item: _citation.page_last / _entity.pdbx_description ..._citation.page_last / _entity.pdbx_description / _entity_name_com.name / _entity_src_gen.gene_src_common_name
Revision 1.4Jan 31, 2024Group: 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: Nucleotide triphosphate diphosphatase NUDT15
hetero molecules


Theoretical massNumber of molelcules
Total (without water)19,0153
Polymers18,6351
Non-polymers3802
Water1,02757
1
A: Nucleotide triphosphate diphosphatase NUDT15
hetero molecules

A: Nucleotide triphosphate diphosphatase NUDT15
hetero molecules


Theoretical massNumber of molelcules
Total (without water)38,0306
Polymers37,2702
Non-polymers7604
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
crystal symmetry operation7_555y,x,-z1
Buried area3430 Å2
ΔGint-36 kcal/mol
Surface area13730 Å2
MethodPISA
Unit cell
Length a, b, c (Å)48.602, 48.602, 134.399
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number96
Space group name H-MP43212
Space group name HallP4nw2abw
Symmetry operation#1: x,y,z
#2: -y+1/2,x+1/2,z+3/4
#3: y+1/2,-x+1/2,z+1/4
#4: x+1/2,-y+1/2,-z+1/4
#5: -x+1/2,y+1/2,-z+3/4
#6: -x,-y,z+1/2
#7: y,x,-z
#8: -y,-x,-z+1/2

-
Components

#1: Protein Nucleotide triphosphate diphosphatase NUDT15 / MutT homolog 2 / MTH2 / Nucleoside diphosphate-linked moiety X motif 15 / Nudix motif 15 / ...MutT homolog 2 / MTH2 / Nucleoside diphosphate-linked moiety X motif 15 / Nudix motif 15 / Nucleoside diphosphate-linked to another moiety X hydrolase 15 / Nudix hydrolase 15


Mass: 18635.002 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: NUDT15, MTH2 / Production host: Escherichia coli BL21(DE3) (bacteria) / References: UniProt: Q9NV35, nucleotide diphosphatase
#2: Chemical ChemComp-RTW / 2-azanyl-9-cyclohexyl-8-(2-methoxyphenyl)-3~{H}-purine-6-thione / TH8321


Mass: 355.457 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C18H21N5OS / Feature type: SUBJECT OF INVESTIGATION
#3: Chemical ChemComp-MG / MAGNESIUM ION


Mass: 24.305 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: Mg
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 57 / Source method: isolated from a natural source / Formula: H2O
Has ligand of interestY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.13 Å3/Da / Density % sol: 42.24 %
Crystal growTemperature: 277 K / Method: vapor diffusion, hanging drop
Details: 0.1 M Tris pH 8.0, 0.2 M sodium acetate, 29.5% PEG 4000

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: MAX IV / Beamline: BioMAX / Wavelength: 0.7749 Å
DetectorType: DECTRIS EIGER X 16M / Detector: PIXEL / Date: Feb 20, 2019
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.7749 Å / Relative weight: 1
ReflectionResolution: 2.35→45.71 Å / Num. obs: 7239 / % possible obs: 99.48 % / Redundancy: 15.9 % / Biso Wilson estimate: 39.67 Å2 / CC1/2: 0.997 / CC star: 0.999 / Rmerge(I) obs: 0.2083 / Rrim(I) all: 0.2152 / Net I/σ(I): 11.05
Reflection shellResolution: 2.35→2.437 Å / Redundancy: 16.4 % / Rmerge(I) obs: 1.168 / Mean I/σ(I) obs: 1.64 / Num. unique obs: 713 / CC1/2: 0.798 / CC star: 0.942 / Rrim(I) all: 1.206 / % possible all: 99.03

-
Processing

Software
NameVersionClassification
PHENIX1.18.2_3874refinement
DIALS3.1.0data reduction
DIALS3.1.0data scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 5LPG

5lpg


Resolution: 2.35→45.71 Å / SU ML: 0.2214 / Cross valid method: FREE R-VALUE / σ(F): 1.35 / Phase error: 22.733
Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
RfactorNum. reflection% reflection
Rfree0.2369 700 9.72 %
Rwork0.1964 6501 -
obs0.2003 7201 99.48 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso mean: 43.87 Å2
Refinement stepCycle: LAST / Resolution: 2.35→45.71 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms1247 0 26 57 1330
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.00791325
X-RAY DIFFRACTIONf_angle_d1.30671803
X-RAY DIFFRACTIONf_chiral_restr0.0786179
X-RAY DIFFRACTIONf_plane_restr0.0042234
X-RAY DIFFRACTIONf_dihedral_angle_d14.1186477
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
2.35-2.530.26141440.25441240X-RAY DIFFRACTION98.86
2.53-2.790.28861280.24241263X-RAY DIFFRACTION99.14
2.79-3.190.29981560.22791270X-RAY DIFFRACTION99.65
3.19-4.020.2561250.19051322X-RAY DIFFRACTION99.79
4.02-45.710.17981470.16481406X-RAY DIFFRACTION99.87
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)
14.88193015299-1.631844286470.3286476777241.26433968394-1.052213612363.455617019840.0423047898372-0.469311023246-0.596508720332-0.1241057993130.0981900298690.2769120755970.332538214980.0652344637420.01341909708820.286608212235-0.035780201027-0.05623281774760.2752601209950.04334522429150.34462392857913.2317394341-3.97277339866.98801940508
23.64099255906-1.20083324540.01519047262291.86860312545-0.6237090317422.432720150040.0475074674038-0.228903471588-0.477804109679-0.3462983847830.04867091506460.1226858216640.4336927831820.2186106701540.0007991952801930.4085548739870.0316091629853-0.05255678195990.2679439883830.02659808512630.3539434952917.1216036971-7.509512593922.71747108911
32.05662182848-1.67675319732-0.05388701795712.27195183836-1.150453505611.552605837580.2232178689710.269031433320.0924133277189-0.239402464277-0.25620140622-0.1500986628460.1850286832330.2736255543527.04143630959E-70.352396844031-0.0189426548597-0.004572852453170.380364800813-0.01289188102840.36460511648616.43423989245.86375011978-4.7987439321
Refinement TLS group

Refine-ID: X-RAY DIFFRACTION / Auth asym-ID: A / Label asym-ID: A

IDRefine TLS-IDSelection detailsAuth seq-IDLabel seq-ID
11(chain A and resid 9:83)9 - 831 - 76
22(chain A and resid 84:138)84 - 13877 - 131
33(chain A and resid 139:164)139 - 164132 - 157

+
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://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