[English] 日本語
Yorodumi
- PDB-6jvl: Crystal structure of human MTH1 in complex with compound MI1014 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6jvl
TitleCrystal structure of human MTH1 in complex with compound MI1014
Components7,8-dihydro-8-oxoguanine triphosphatase
KeywordsHYDROLASE / MTH1 / Oxidative DNA damage / 8-oxo-dGTP / Inhibitor development
Function / homology
Function and homology information


2-hydroxy-ATP hydrolase activity / 2-hydroxy-dATP hydrolase activity / N6-methyl-(d)ATP hydrolase activity / O6-methyl-dGTP hydrolase activity / 2-hydroxy-dATP diphosphatase / dATP diphosphatase activity / ATP diphosphatase activity / 8-oxo-7,8-dihydrodeoxyguanosine triphosphate pyrophosphatase activity / 8-oxo-7,8-dihydroguanosine triphosphate pyrophosphatase activity / hydrolase activity, acting on acid anhydrides, in phosphorus-containing anhydrides ...2-hydroxy-ATP hydrolase activity / 2-hydroxy-dATP hydrolase activity / N6-methyl-(d)ATP hydrolase activity / O6-methyl-dGTP hydrolase activity / 2-hydroxy-dATP diphosphatase / dATP diphosphatase activity / ATP diphosphatase activity / 8-oxo-7,8-dihydrodeoxyguanosine triphosphate pyrophosphatase activity / 8-oxo-7,8-dihydroguanosine triphosphate pyrophosphatase activity / hydrolase activity, acting on acid anhydrides, in phosphorus-containing anhydrides / DNA protection / Phosphate bond hydrolysis by NUDT proteins / purine nucleoside catabolic process / snoRNA binding / Hydrolases; Acting on acid anhydrides; In phosphorus-containing anhydrides / response to cadmium ion / acrosomal vesicle / male gonad development / nuclear membrane / response to oxidative stress / mitochondrial matrix / DNA repair / mitochondrion / extracellular space / nucleus / metal ion binding / cytosol / cytoplasm
Similarity search - Function
Oxidized purine nucleoside triphosphate / NUDIX hydrolase / NUDIX hydrolase, conserved site / Nudix box signature. / NUDIX domain / Nudix hydrolase domain profile. / NUDIX hydrolase domain / NUDIX hydrolase-like domain superfamily
Similarity search - Domain/homology
Chem-CG0 / Oxidized purine nucleoside triphosphate hydrolase
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.9 Å
AuthorsPeng, C. / Li, Y.H. / Cheng, Y.S.
CitationJournal: Bioorg.Chem. / Year: 2021
Title: Inhibitor development of MTH1 via high-throughput screening with fragment based library and MTH1 substrate binding cavity.
Authors: Peng, C. / Li, Y.H. / Yu, C.W. / Cheng, Z.H. / Liu, J.R. / Hsu, J.L. / Hsin, L.W. / Huang, C.T. / Juan, H.F. / Chern, J.W. / Cheng, Y.S.
History
DepositionApr 17, 2019Deposition site: PDBJ / Processing site: PDBJ
Revision 1.0Oct 28, 2020Provider: repository / Type: Initial release
Revision 1.1May 12, 2021Group: Database references / Category: citation / citation_author
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_ASTM / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.journal_volume / _citation.page_first / _citation.page_last / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _citation.year
Revision 1.2Mar 27, 2024Group: Data collection / Database references / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / struct_ncs_dom_lim
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _struct_ncs_dom_lim.beg_auth_comp_id / _struct_ncs_dom_lim.beg_label_asym_id / _struct_ncs_dom_lim.beg_label_comp_id / _struct_ncs_dom_lim.beg_label_seq_id / _struct_ncs_dom_lim.end_auth_comp_id / _struct_ncs_dom_lim.end_label_asym_id / _struct_ncs_dom_lim.end_label_comp_id / _struct_ncs_dom_lim.end_label_seq_id

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: 7,8-dihydro-8-oxoguanine triphosphatase
B: 7,8-dihydro-8-oxoguanine triphosphatase
hetero molecules


Theoretical massNumber of molelcules
Total (without water)36,2193
Polymers35,9432
Non-polymers2761
Water4,684260
1
A: 7,8-dihydro-8-oxoguanine triphosphatase
hetero molecules


Theoretical massNumber of molelcules
Total (without water)18,2482
Polymers17,9711
Non-polymers2761
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
2
B: 7,8-dihydro-8-oxoguanine triphosphatase


Theoretical massNumber of molelcules
Total (without water)17,9711
Polymers17,9711
Non-polymers00
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Unit cell
Length a, b, c (Å)59.244, 67.227, 79.583
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number19
Space group name H-MP212121
Noncrystallographic symmetry (NCS)NCS domain:
IDEns-IDDetails
11(chain A and (resid 3 through 13 or resid 18 through 156))
21(chain B and resid 3 through 156)

NCS domain segments:

Ens-ID: 1

Dom-IDComponent-IDBeg auth comp-IDBeg label comp-IDEnd auth comp-IDEnd label comp-IDSelection detailsAuth asym-IDLabel asym-IDAuth seq-IDLabel seq-ID
11ALAALALEULEU(chain A and (resid 3 through 13 or resid 18 through 156))AA3 - 133 - 13
12VALVALVALVAL(chain A and (resid 3 through 13 or resid 18 through 156))AA18 - 15618 - 156
21ALAALAVALVAL(chain B and resid 3 through 156)BB3 - 1563 - 156

-
Components

#1: Protein 7,8-dihydro-8-oxoguanine triphosphatase / 2-hydroxy-dATP diphosphatase / 8-oxo-dGTPase / Nucleoside diphosphate-linked moiety X motif 1 / Nudix motif 1


Mass: 17971.461 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: NUDT1, MTH1 / Plasmid: pET28a / Production host: Escherichia coli (E. coli) / Strain (production host): Rosetta(DE3)
References: UniProt: P36639, 8-oxo-dGTP diphosphatase, 2-hydroxy-dATP diphosphatase
#2: Chemical ChemComp-CG0 / N4-cyclopropyl-5-ethyl-6-(4-methylpiperazin-1-yl)pyrimidine-2,4-diamine


Mass: 276.381 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C14H24N6
#3: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 260 / Source method: isolated from a natural source / Formula: H2O

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.26 Å3/Da / Density % sol: 45.5 % / Mosaicity: 0.376 °
Crystal growTemperature: 298 K / Method: evaporation / pH: 3.75
Details: 30% PEG 6000, 200 mM Lithium sulphate, 100 mM Sodium acetate pH 3.75

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: NSRRC / Beamline: BL13B1 / Wavelength: 1 Å
DetectorType: RAYONIX MX300HE / Detector: CCD / Date: Oct 2, 2018 / Details: mirrors
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 1.9→30 Å / Num. obs: 25739 / % possible obs: 99.6 % / Redundancy: 4 % / Rmerge(I) obs: 0.057 / Rpim(I) all: 0.033 / Rrim(I) all: 0.066 / Χ2: 1.069 / Net I/σ(I): 14.1
Reflection shell

Diffraction-ID: 1

Resolution (Å)Redundancy (%)Rmerge(I) obsNum. unique obsCC1/2Rpim(I) allRrim(I) allΧ2% possible all
1.9-1.973.90.31725280.9060.1830.3681.09999.5
1.97-2.053.90.22125500.9470.1260.2551.09499.6
2.05-2.1440.16525160.9760.0920.1891.09999.8
2.14-2.2540.12925400.9840.0730.1491.089100
2.25-2.3940.11725530.9880.0660.1351.0799.8
2.39-2.5840.0925680.9930.0510.1031.07899.9
2.58-2.8440.06625770.9960.0370.0761.03100
2.84-3.2540.04825750.9980.0270.0551.06699.8
3.25-4.093.90.04126250.9960.0240.0481.00599.8
4.09-303.70.02927070.9980.0170.0341.06897.8

-
Processing

Software
NameVersionClassification
HKL-2000data scaling
PHENIX1.14_3260refinement
PDB_EXTRACT3.25data extraction
HKL-2000data reduction
PHENIXphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 1.9→27.761 Å / SU ML: 0.19 / Cross valid method: THROUGHOUT / σ(F): 0 / Phase error: 22.89
RfactorNum. reflection% reflection
Rfree0.2473 1951 7.77 %
Rwork0.1933 --
obs0.1975 25107 97.22 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å
Displacement parametersBiso max: 91.8 Å2 / Biso mean: 28.278 Å2 / Biso min: 9.64 Å2
Refinement stepCycle: final / Resolution: 1.9→27.761 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2476 0 20 260 2756
Biso mean--48.48 36.43 -
Num. residues----305
Refine LS restraints NCS
Ens-IDDom-IDAuth asym-IDNumberRefine-IDRmsType
11A904X-RAY DIFFRACTION2.469TORSIONAL
12B904X-RAY DIFFRACTION2.469TORSIONAL
LS refinement shell

Refine-ID: X-RAY DIFFRACTION / Rfactor Rfree error: 0 / Total num. of bins used: 14

Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkNum. reflection all% reflection obs (%)
1.8967-1.94420.2631250.22441501162689
1.9442-1.99670.27461370.20441576171395
1.9967-2.05540.26551340.19471593172796
2.0554-2.12180.23431340.18541639177397
2.1218-2.19760.22081390.17751646178598
2.1976-2.28550.21941370.1791622175997
2.2855-2.38950.2611390.19051668180798
2.3895-2.51540.25261390.20391642178198
2.5154-2.67290.25881410.20051671181298
2.6729-2.8790.26661400.21571662180298
2.879-3.16840.29281440.21231699184399
3.1684-3.6260.26781440.181717161860100
3.626-4.56510.20891470.16051729187699
4.5651-27.76420.23441510.2141792194398
Refinement TLS params.Method: refined / Origin x: 16.0722 Å / Origin y: 0.7518 Å / Origin z: -9.9328 Å
111213212223313233
T0.1438 Å20.0078 Å20.0004 Å2-0.1354 Å20.012 Å2--0.1032 Å2
L1.9351 °20.4478 °20.0602 °2-0.6125 °2-0.0585 °2--0.1395 °2
S0.0125 Å °-0.1291 Å °-0.2421 Å °-0.0409 Å °0.0017 Å °-0.0085 Å °-0.0119 Å °-0.0453 Å °-0.0189 Å °
Refinement TLS groupSelection details: all

+
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