[English] 日本語
Yorodumi
- PDB-6ws0: Rational drug design of phenazopyridine derivatives as novel inhi... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6ws0
TitleRational drug design of phenazopyridine derivatives as novel inhibitors of Rev1-CT
Components
  • DNA polymerase zeta catalytic subunit
  • DNA repair protein REV1
  • Mitotic spindle assembly checkpoint protein MAD2B
KeywordsPROTEIN BINDING/Transferase / scaffold / translesion synethesis / DNA damage response / DNA damage tolerance / PROTEIN BINDING-Transferase complex
Function / homology
Function and homology information


somatic diversification of immunoglobulins involved in immune response / DNA damage response, signal transduction resulting in transcription / deoxycytidyl transferase activity / telomere maintenance in response to DNA damage / negative regulation of transcription regulatory region DNA binding / zeta DNA polymerase complex / positive regulation of isotype switching / positive regulation of extracellular matrix assembly / negative regulation of transcription by competitive promoter binding / negative regulation of cell-cell adhesion mediated by cadherin ...somatic diversification of immunoglobulins involved in immune response / DNA damage response, signal transduction resulting in transcription / deoxycytidyl transferase activity / telomere maintenance in response to DNA damage / negative regulation of transcription regulatory region DNA binding / zeta DNA polymerase complex / positive regulation of isotype switching / positive regulation of extracellular matrix assembly / negative regulation of transcription by competitive promoter binding / negative regulation of cell-cell adhesion mediated by cadherin / negative regulation of epithelial to mesenchymal transition / JUN kinase binding / negative regulation of ubiquitin protein ligase activity / error-free translesion synthesis / mitotic spindle assembly checkpoint signaling / positive regulation of double-strand break repair via nonhomologous end joining / negative regulation of double-strand break repair via homologous recombination / error-prone translesion synthesis / positive regulation of epithelial to mesenchymal transition / response to UV / Translesion synthesis by REV1 / Translesion synthesis by POLK / Translesion synthesis by POLI / actin filament organization / regulation of cell growth / Termination of translesion DNA synthesis / double-strand break repair via homologous recombination / negative regulation of canonical Wnt signaling pathway / negative regulation of protein catabolic process / negative regulation of DNA-binding transcription factor activity / DNA-templated DNA replication / spindle / double-strand break repair / Transferases; Transferring phosphorus-containing groups; Nucleotidyltransferases / positive regulation of peptidyl-serine phosphorylation / site of double-strand break / chromosome / 4 iron, 4 sulfur cluster binding / RNA polymerase II-specific DNA-binding transcription factor binding / DNA replication / damaged DNA binding / DNA-directed DNA polymerase / DNA-directed DNA polymerase activity / cell division / nucleotide binding / chromatin / nucleolus / positive regulation of DNA-templated transcription / negative regulation of transcription by RNA polymerase II / DNA binding / nucleoplasm / metal ion binding / nucleus / cytoplasm
Similarity search - Function
DNA repair protein Rev1, C-terminal / Rev1, C-terminal domain superfamily / : / DNA repair protein REV1 C-terminal domain / Domain of unknown function DUF4683 / Domain of unknown function (DUF4683) / DNA polymerase zeta catalytic subunit / HUWE1/Rev1, ubiquitin binding region / Ubiquitin binding region / DNA repair protein Rev1 ...DNA repair protein Rev1, C-terminal / Rev1, C-terminal domain superfamily / : / DNA repair protein REV1 C-terminal domain / Domain of unknown function DUF4683 / Domain of unknown function (DUF4683) / DNA polymerase zeta catalytic subunit / HUWE1/Rev1, ubiquitin binding region / Ubiquitin binding region / DNA repair protein Rev1 / C4-type zinc-finger of DNA polymerase delta / C4-type zinc-finger of DNA polymerase delta / Mad2-like / HORMA domain / HORMA domain / HORMA domain profile. / HORMA domain superfamily / DNApol eta/Rev1, HhH motif / DNA polymerase family B, thumb domain / DNA polymerase family B signature. / DNA-directed DNA polymerase, family B, conserved site / DNA polymerase family B / DNA polymerase family B, exonuclease domain / DNA-directed DNA polymerase, family B, exonuclease domain / DNA-directed DNA polymerase, family B, multifunctional domain / DNA polymerase, palm domain superfamily / DNA polymerase type-B family / DNA-directed DNA polymerase, family B / BRCA1 C Terminus (BRCT) domain / DNA polymerase, Y-family, little finger domain / impB/mucB/samB family C-terminal domain / UmuC domain / DNA polymerase, Y-family, little finger domain superfamily / impB/mucB/samB family / UmuC domain profile. / breast cancer carboxy-terminal domain / BRCT domain profile. / BRCT domain / BRCT domain superfamily / Ribonuclease H superfamily / Ribonuclease H-like superfamily / Reverse transcriptase/Diguanylate cyclase domain / DNA/RNA polymerase superfamily
Similarity search - Domain/homology
DNA polymerase zeta catalytic subunit / DNA repair protein REV1 / Mitotic spindle assembly checkpoint protein MAD2B
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.24 Å
AuthorsMcPherson, K.S. / Korzhnev, D.M.
Funding support United States, 1items
OrganizationGrant numberCountry
National Institutes of Health/National Cancer Institute (NIH/NCI)R01CA233959 United States
CitationJournal: Chemmedchem / Year: 2021
Title: Structure-Based Drug Design of Phenazopyridine Derivatives as Inhibitors of Rev1 Interactions in Translesion Synthesis.
Authors: McPherson, K.S. / Zaino, A.M. / Dash, R.C. / Rizzo, A.A. / Li, Y. / Hao, B. / Bezsonova, I. / Hadden, M.K. / Korzhnev, D.M.
History
DepositionApr 30, 2020Deposition site: RCSB / Processing site: RCSB
Revision 1.0Dec 23, 2020Provider: repository / Type: Initial release
Revision 1.1Jul 7, 2021Group: Database references / Category: citation / citation_author
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _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 1.2Oct 18, 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
HHH: DNA repair protein REV1
CCC: Mitotic spindle assembly checkpoint protein MAD2B
ZZZ: DNA polymerase zeta catalytic subunit


Theoretical massNumber of molelcules
Total (without water)42,7453
Polymers42,7453
Non-polymers00
Water19811
1
CCC: Mitotic spindle assembly checkpoint protein MAD2B
ZZZ: DNA polymerase zeta catalytic subunit

HHH: DNA repair protein REV1


Theoretical massNumber of molelcules
Total (without water)42,7453
Polymers42,7453
Non-polymers00
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
crystal symmetry operation5_664x-y+1,-y+1,-z-1/31
Buried area4060 Å2
ΔGint-31 kcal/mol
Surface area14710 Å2
MethodPISA
Unit cell
Length a, b, c (Å)69.376, 69.376, 106.391
Angle α, β, γ (deg.)90.000, 90.000, 120.000
Int Tables number152
Space group name H-MP3121

-
Components

#1: Protein DNA repair protein REV1 / / Alpha integrin-binding protein 80 / AIBP80 / Rev1-like terminal deoxycytidyl transferase


Mass: 11011.666 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: REV1, REV1L / Production host: Escherichia coli BL21 (bacteria)
References: UniProt: Q9UBZ9, Transferases; Transferring phosphorus-containing groups; Nucleotidyltransferases
#2: Protein Mitotic spindle assembly checkpoint protein MAD2B / Mitotic arrest deficient 2-like protein 2 / MAD2-like protein 2 / REV7 homolog / hREV7


Mass: 26101.236 Da / Num. of mol.: 1 / Mutation: R124A
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: MAD2L2, MAD2B, REV7 / Production host: Escherichia coli (E. coli) / References: UniProt: Q9UI95
#3: Protein DNA polymerase zeta catalytic subunit / Protein reversionless 3-like / hREV3


Mass: 5632.319 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: REV3L, POLZ, REV3 / Production host: Escherichia coli (E. coli) / References: UniProt: O60673, DNA-directed DNA polymerase
#4: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 11 / 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: 1.73 Å3/Da / Density % sol: 28.86 %
Crystal growTemperature: 293 K / Method: vapor diffusion, hanging drop / Details: 162 mM triammonium citrate and 18% w/v PEG 3350

-
Data collection

DiffractionMean temperature: 280 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: NSLS-II / Beamline: 17-ID-1 / Wavelength: 0.97934 Å
DetectorType: DECTRIS EIGER2 X 9M / Detector: PIXEL / Date: Jun 25, 2019
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.97934 Å / Relative weight: 1
ReflectionResolution: 2.238→29.073 Å / Num. obs: 14749 / % possible obs: 99.4 % / Redundancy: 9 % / CC1/2: 0.997 / Rrim(I) all: 0.107 / Net I/σ(I): 12.9
Reflection shellResolution: 2.238→2.31 Å / Num. unique obs: 1267 / CC1/2: 0.774

-
Processing

Software
NameVersionClassification
REFMAC5.8.0253refinement
DIALSdata reduction
Aimlessdata scaling
MOLREPphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 3vu7

3vu7


Resolution: 2.24→29.07 Å / Cor.coef. Fo:Fc: 0.953 / Cor.coef. Fo:Fc free: 0.949 / Cross valid method: FREE R-VALUE / ESU R: 0.367 / ESU R Free: 0.217
Details: Hydrogens have been added in their riding positions
RfactorNum. reflection% reflection
Rfree0.221 771 5.239 %
Rwork0.204 13946 -
all0.205 --
obs-14717 99.439 %
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK BULK SOLVENT
Displacement parametersBiso mean: 47.319 Å2
Baniso -1Baniso -2Baniso -3
1--0.587 Å2-0.293 Å20 Å2
2---0.587 Å20 Å2
3---1.904 Å2
Refinement stepCycle: LAST / Resolution: 2.24→29.07 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2470 0 0 11 2481
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.010.0132525
X-RAY DIFFRACTIONr_bond_other_d0.0340.0172454
X-RAY DIFFRACTIONr_angle_refined_deg1.8241.6373422
X-RAY DIFFRACTIONr_angle_other_deg2.2891.5765702
X-RAY DIFFRACTIONr_dihedral_angle_1_deg8.0115302
X-RAY DIFFRACTIONr_dihedral_angle_2_deg31.96223.73126
X-RAY DIFFRACTIONr_dihedral_angle_3_deg16.73815481
X-RAY DIFFRACTIONr_dihedral_angle_4_deg19.0431512
X-RAY DIFFRACTIONr_chiral_restr0.0870.2336
X-RAY DIFFRACTIONr_gen_planes_refined0.0090.022709
X-RAY DIFFRACTIONr_gen_planes_other0.0110.02467
X-RAY DIFFRACTIONr_nbd_refined0.2220.2550
X-RAY DIFFRACTIONr_symmetry_nbd_other0.2250.22281
X-RAY DIFFRACTIONr_nbtor_refined0.1730.21176
X-RAY DIFFRACTIONr_symmetry_nbtor_other0.0760.21072
X-RAY DIFFRACTIONr_xyhbond_nbd_refined0.1470.254
X-RAY DIFFRACTIONr_symmetry_xyhbond_nbd_other0.0160.22
X-RAY DIFFRACTIONr_symmetry_nbd_refined0.1530.222
X-RAY DIFFRACTIONr_nbd_other0.2530.294
X-RAY DIFFRACTIONr_symmetry_xyhbond_nbd_refined0.1940.27
X-RAY DIFFRACTIONr_mcbond_it4.6534.711220
X-RAY DIFFRACTIONr_mcbond_other4.6474.7061219
X-RAY DIFFRACTIONr_mcangle_it6.9517.021518
X-RAY DIFFRACTIONr_mcangle_other6.957.0261519
X-RAY DIFFRACTIONr_scbond_it5.3375.3211305
X-RAY DIFFRACTIONr_scbond_other5.3355.3251306
X-RAY DIFFRACTIONr_scangle_it8.3437.7111903
X-RAY DIFFRACTIONr_scangle_other8.3417.7151904
X-RAY DIFFRACTIONr_lrange_it11.13654.9822742
X-RAY DIFFRACTIONr_lrange_other11.13555.0172743
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
2.24-2.2960.352640.339911X-RAY DIFFRACTION93.65
2.296-2.3590.314580.2851015X-RAY DIFFRACTION100
2.359-2.4270.301560.297947X-RAY DIFFRACTION100
2.427-2.5020.271400.254962X-RAY DIFFRACTION100
2.502-2.5840.227380.211922X-RAY DIFFRACTION100
2.584-2.6740.25460.248877X-RAY DIFFRACTION100
2.674-2.7750.25480.204870X-RAY DIFFRACTION100
2.775-2.8880.238490.185811X-RAY DIFFRACTION100
2.888-3.0170.321340.2813X-RAY DIFFRACTION100
3.017-3.1640.222500.214754X-RAY DIFFRACTION100
3.164-3.3350.27470.199707X-RAY DIFFRACTION100
3.335-3.5370.19430.175679X-RAY DIFFRACTION100
3.537-3.7810.227280.169650X-RAY DIFFRACTION100
3.781-4.0830.177340.174619X-RAY DIFFRACTION100
4.083-4.4720.174360.165542X-RAY DIFFRACTION100
4.472-4.9990.192240.149526X-RAY DIFFRACTION100
4.999-5.770.15921461X-RAY DIFFRACTION100
5.77-7.0620.272320.241386X-RAY DIFFRACTION100
7-9.90.1849183X-RAY DIFFRACTION94.5813
7.062-9.9650.236180.192311X-RAY DIFFRACTION100

+
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