[English] 日本語
Yorodumi
- PDB-6us3: MTH1 in complex with compound 4 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6us3
TitleMTH1 in complex with compound 4
Components7,8-dihydro-8-oxoguanine triphosphatase
KeywordsHYDROLASE/HYDROLASE INHIBITOR / Hydrolase / NUDT1 / Nudix hydrolase / inhibitor / HYDROLASE-HYDROLASE INHIBITOR complex
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 / DNA protection ...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 / DNA protection / hydrolase activity, acting on acid anhydrides, in phosphorus-containing anhydrides / 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 / Nucleoside Triphosphate Pyrophosphohydrolase / Nucleoside Triphosphate Pyrophosphohydrolase / NUDIX hydrolase, conserved site / Nudix box signature. / NUDIX domain / Nudix hydrolase domain profile. / NUDIX hydrolase domain / NUDIX hydrolase-like domain superfamily ...Oxidized purine nucleoside triphosphate / NUDIX hydrolase / Nucleoside Triphosphate Pyrophosphohydrolase / Nucleoside Triphosphate Pyrophosphohydrolase / NUDIX hydrolase, conserved site / Nudix box signature. / NUDIX domain / Nudix hydrolase domain profile. / NUDIX hydrolase domain / NUDIX hydrolase-like domain superfamily / Alpha-Beta Complex / Alpha Beta
Similarity search - Domain/homology
Chem-8JF / Oxidized purine nucleoside triphosphate hydrolase
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.47028917623 Å
AuthorsNewby, Z.E.R. / Lansdon, E.B.
CitationJournal: Acs Med.Chem.Lett. / Year: 2020
Title: Discovery of Potent and Selective MTH1 Inhibitors for Oncology: Enabling Rapid Target (In)Validation.
Authors: Farand, J. / Kropf, J.E. / Blomgren, P. / Xu, J. / Schmitt, A.C. / Newby, Z.E. / Wang, T. / Murakami, E. / Barauskas, O. / Sudhamsu, J. / Feng, J.Y. / Niedziela-Majka, A. / Schultz, B.E. / ...Authors: Farand, J. / Kropf, J.E. / Blomgren, P. / Xu, J. / Schmitt, A.C. / Newby, Z.E. / Wang, T. / Murakami, E. / Barauskas, O. / Sudhamsu, J. / Feng, J.Y. / Niedziela-Majka, A. / Schultz, B.E. / Schwartz, K. / Viatchenko-Karpinski, S. / Kornyeyev, D. / Kashishian, A. / Fan, P. / Chen, X. / Lansdon, E.B. / Ports, M.O. / Currie, K.S. / Watkins, W.J. / Notte, G.T.
History
DepositionOct 24, 2019Deposition site: RCSB / Processing site: RCSB
Revision 1.0Apr 1, 2020Provider: repository / Type: Initial release
Revision 1.1Oct 11, 2023Group: Data collection / Database references / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

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


Theoretical massNumber of molelcules
Total (without water)18,5452
Polymers18,2541
Non-polymers2911
Water2,324129
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area0 Å2
ΔGint0 kcal/mol
Surface area7900 Å2
MethodPISA
Unit cell
Length a, b, c (Å)36.333, 59.868, 66.523
Angle α, β, γ (deg.)90.0, 90.0, 90.0
Int Tables number18
Space group name H-MP22121
Space group name HallP22ab(z,x,y)
Symmetry operation#1: x,y,z
#2: x,-y,-z
#3: -x,y+1/2,-z+1/2
#4: -x,-y+1/2,z+1/2

-
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: 18253.736 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: NUDT1, MTH1 / Production host: Escherichia coli (E. coli)
References: UniProt: P36639, 8-oxo-dGTP diphosphatase, 2-hydroxy-dATP diphosphatase
#2: Chemical ChemComp-8JF / N-[5-(2,3-dimethylphenyl)-1,6-naphthyridin-7-yl]acetamide


Mass: 291.347 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C18H17N3O / Feature type: SUBJECT OF INVESTIGATION
#3: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 129 / 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: 1.98 Å3/Da / Density % sol: 37.93 %
Crystal growTemperature: 293 K / Method: vapor diffusion, hanging drop
Details: 30% PEG 6000, 0.1M sodium acetate pH 4.0, 0.2M lithium sulfate

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: ALS / Beamline: 5.0.1 / Wavelength: 0.97741 Å
DetectorType: ADSC QUANTUM 315r / Detector: CCD / Date: Sep 4, 2014
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.97741 Å / Relative weight: 1
ReflectionResolution: 1.47→50 Å / Num. obs: 25250 / % possible obs: 99.4 % / Redundancy: 4.9 % / Biso Wilson estimate: 12.848321994 Å2 / Rmerge(I) obs: 0.053 / Net I/σ(I): 23.8
Reflection shellResolution: 1.47→1.5 Å / Rmerge(I) obs: 0.514 / Num. unique obs: 1256

-
Processing

Software
NameVersionClassification
PHENIX1.9_1692refinement
HKL-2000data reduction
HKL-2000data scaling
PHENIXphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 3ZR0

3zr0


Resolution: 1.47028917623→44.5004320268 Å / SU ML: 0.135498224058 / Cross valid method: THROUGHOUT / σ(F): 0.250482772498 / Phase error: 19.9036467953
RfactorNum. reflection% reflection
Rfree0.222219277267 2000 8.34237090181 %
Rwork0.1865002798 --
obs0.189437603238 23974 94.4564831961 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å
Displacement parametersBiso mean: 16.9610286914 Å2
Refinement stepCycle: LAST / Resolution: 1.47028917623→44.5004320268 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms1254 0 22 129 1405
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.007921898920811340
X-RAY DIFFRACTIONf_angle_d1.191494809461820
X-RAY DIFFRACTIONf_chiral_restr0.0558516738653187
X-RAY DIFFRACTIONf_plane_restr0.00749587046867236
X-RAY DIFFRACTIONf_dihedral_angle_d13.5436205918497
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
1.4703-1.50710.2689087402061220.213218044931347X-RAY DIFFRACTION82.9474872953
1.5071-1.54780.2586263543051300.2168581465831428X-RAY DIFFRACTION87.5772906127
1.5478-1.59340.2335695793041350.1898284466441471X-RAY DIFFRACTION89.8712926693
1.5934-1.64480.2384939932021370.1824468383851503X-RAY DIFFRACTION92.29037704
1.6448-1.70360.227774688591410.186801766031557X-RAY DIFFRACTION94.1763727121
1.7036-1.77180.2342121360281420.1851985818121559X-RAY DIFFRACTION95.7231288689
1.7718-1.85240.2366384915341440.1787719462141584X-RAY DIFFRACTION95.8934517203
1.8524-1.95010.2172529374991450.1801171900581587X-RAY DIFFRACTION96.7057509771
1.9501-2.07230.217257976531470.176493016341623X-RAY DIFFRACTION98.3333333333
2.0723-2.23230.2105193354811490.1796458426561625X-RAY DIFFRACTION98.0652294085
2.2323-2.45690.2179037356441470.1885290877511625X-RAY DIFFRACTION97.0427163198
2.4569-2.81240.2262219975171500.2001937819131640X-RAY DIFFRACTION97.2826086957
2.8124-3.54310.2080484993911510.1862230037531661X-RAY DIFFRACTION97.9459459459
3.5431-44.50043202680.2204419679151600.1831889062541764X-RAY DIFFRACTION97.8636826043

+
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