[English] 日本語
Yorodumi
- PDB-7ont: PARP1 catalytic domain in complex with a selective pyridine carbo... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 7ont
TitlePARP1 catalytic domain in complex with a selective pyridine carboxamide-based inhibitor (compound 22)
ComponentsPoly [ADP-ribose] polymerase 1
KeywordsTRANSFERASE / PARP inhibitor / selectivity / structure-based drug design / synthetic lethal therapy / oncology
Function / homology
Function and homology information


positive regulation of myofibroblast differentiation / regulation of base-excision repair / NAD+-histone H2BS6 serine ADP-ribosyltransferase activity / NAD+-histone H3S10 serine ADP-ribosyltransferase activity / NAD+-histone H2BE35 glutamate ADP-ribosyltransferase activity / negative regulation of ATP biosynthetic process / NAD+-protein-tyrosine ADP-ribosyltransferase activity / NAD+-protein-histidine ADP-ribosyltransferase activity / regulation of circadian sleep/wake cycle, non-REM sleep / vRNA Synthesis ...positive regulation of myofibroblast differentiation / regulation of base-excision repair / NAD+-histone H2BS6 serine ADP-ribosyltransferase activity / NAD+-histone H3S10 serine ADP-ribosyltransferase activity / NAD+-histone H2BE35 glutamate ADP-ribosyltransferase activity / negative regulation of ATP biosynthetic process / NAD+-protein-tyrosine ADP-ribosyltransferase activity / NAD+-protein-histidine ADP-ribosyltransferase activity / regulation of circadian sleep/wake cycle, non-REM sleep / vRNA Synthesis / positive regulation of single strand break repair / carbohydrate biosynthetic process / NAD+-protein-serine ADP-ribosyltransferase activity / regulation of catalytic activity / negative regulation of adipose tissue development / NAD DNA ADP-ribosyltransferase activity / DNA ADP-ribosylation / mitochondrial DNA metabolic process / regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway / replication fork reversal / ATP generation from poly-ADP-D-ribose / positive regulation of necroptotic process / transcription regulator activator activity / HDR through MMEJ (alt-NHEJ) / positive regulation of DNA-templated transcription, elongation / signal transduction involved in regulation of gene expression / NAD+ ADP-ribosyltransferase / cellular response to zinc ion / negative regulation of telomere maintenance via telomere lengthening / protein auto-ADP-ribosylation / NAD+-protein-aspartate ADP-ribosyltransferase activity / mitochondrial DNA repair / protein poly-ADP-ribosylation / positive regulation of intracellular estrogen receptor signaling pathway / negative regulation of cGAS/STING signaling pathway / NAD+-protein-glutamate ADP-ribosyltransferase activity / response to aldosterone / positive regulation of mitochondrial depolarization / positive regulation of cardiac muscle hypertrophy / NAD+-protein mono-ADP-ribosyltransferase activity / R-SMAD binding / nuclear replication fork / negative regulation of transcription elongation by RNA polymerase II / protein autoprocessing / site of DNA damage / macrophage differentiation / NAD+ poly-ADP-ribosyltransferase activity / decidualization / Transferases; Glycosyltransferases; Pentosyltransferases / positive regulation of SMAD protein signal transduction / POLB-Dependent Long Patch Base Excision Repair / positive regulation of double-strand break repair via homologous recombination / SUMOylation of DNA damage response and repair proteins / nucleosome binding / protein localization to chromatin / nucleotidyltransferase activity / telomere maintenance / transforming growth factor beta receptor signaling pathway / negative regulation of innate immune response / nuclear estrogen receptor binding / response to gamma radiation / mitochondrion organization / Downregulation of SMAD2/3:SMAD4 transcriptional activity / cellular response to nerve growth factor stimulus / DNA Damage Recognition in GG-NER / protein-DNA complex / protein modification process / positive regulation of protein localization to nucleus / Dual Incision in GG-NER / histone deacetylase binding / Formation of Incision Complex in GG-NER / cellular response to insulin stimulus / cellular response to amyloid-beta / NAD binding / cellular response to UV / nuclear envelope / double-strand break repair / regulation of protein localization / site of double-strand break / cellular response to oxidative stress / transcription regulator complex / RNA polymerase II-specific DNA-binding transcription factor binding / transcription by RNA polymerase II / damaged DNA binding / positive regulation of canonical NF-kappaB signal transduction / chromosome, telomeric region / nuclear body / innate immune response / DNA repair / negative regulation of DNA-templated transcription / apoptotic process / ubiquitin protein ligase binding / DNA damage response / chromatin binding / protein kinase binding / chromatin / nucleolus / enzyme binding / negative regulation of transcription by RNA polymerase II / protein homodimerization activity
Similarity search - Function
Poly(ADP-ribose) polymerase, regulatory domain / Poly(ADP-ribose) Polymerase; domain 1 / Poly [ADP-ribose] polymerase / PADR1 domain / PADR1 domain superfamily / : / PADR1 domain, zinc ribbon fold / PADR1, N-terminal helical domain / PADR1 domain profile. / PADR1 ...Poly(ADP-ribose) polymerase, regulatory domain / Poly(ADP-ribose) Polymerase; domain 1 / Poly [ADP-ribose] polymerase / PADR1 domain / PADR1 domain superfamily / : / PADR1 domain, zinc ribbon fold / PADR1, N-terminal helical domain / PADR1 domain profile. / PADR1 / Zinc finger poly(ADP-ribose) polymerase (PARP)-type signature. / Zinc finger, PARP-type superfamily / Poly(ADP-ribose) polymerase and DNA-Ligase Zn-finger region / Zinc finger poly(ADP-ribose) polymerase (PARP)-type profile. / Poly(ADP-ribose) polymerase and DNA-Ligase Zn-finger region / Zinc finger, PARP-type / : / Poly(ADP-ribose) polymerase, regulatory domain / WGR domain / WGR domain superfamily / WGR domain / WGR domain profile. / Proposed nucleic acid binding domain / Poly(ADP-ribose) polymerase, regulatory domain superfamily / Poly(ADP-ribose) polymerase, regulatory domain / PARP alpha-helical domain profile. / Phosphoenolpyruvate Carboxykinase; domain 3 - #10 / Phosphoenolpyruvate Carboxykinase; domain 3 / BRCA1 C Terminus (BRCT) domain / Poly(ADP-ribose) polymerase catalytic domain / Poly(ADP-ribose) polymerase, catalytic domain / PARP catalytic domain profile. / breast cancer carboxy-terminal domain / BRCT domain profile. / BRCT domain / BRCT domain superfamily / Alpha-Beta Complex / Up-down Bundle / Mainly Alpha / Alpha Beta
Similarity search - Domain/homology
Chem-VKQ / Poly [ADP-ribose] polymerase 1
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.853 Å
AuthorsSchimpl, M. / Balazs, A. / Barratt, D. / Bista, M. / Chuba, M. / Degorce, S.L. / Di Fruscia, P. / Embrey, K. / Ghosh, A. / Gill, S. ...Schimpl, M. / Balazs, A. / Barratt, D. / Bista, M. / Chuba, M. / Degorce, S.L. / Di Fruscia, P. / Embrey, K. / Ghosh, A. / Gill, S. / Gunnarsson, A. / Hande, S. / Hemsley, P. / Heightman, T.D. / Illuzzi, G. / Lane, J. / Larner, C. / Leo, E. / Madin, A. / Martin, S. / McWilliams, L. / Orme, J. / Pachl, F. / Packer, M.J. / Pike, A. / Staniszewska, A.D. / Talbot, V. / Underwood, E. / Varnes, G.J. / Zhang, A. / Zheng, X. / Johannes, J.W.
Funding support United Kingdom, 1items
OrganizationGrant numberCountry
Not funded United Kingdom
CitationJournal: J.Med.Chem. / Year: 2021
Title: Discovery of 5-{4-[(7-Ethyl-6-oxo-5,6-dihydro-1,5-naphthyridin-3-yl)methyl]piperazin-1-yl}- N -methylpyridine-2-carboxamide (AZD5305): A PARP1-DNA Trapper with High Selectivity for PARP1 over ...Title: Discovery of 5-{4-[(7-Ethyl-6-oxo-5,6-dihydro-1,5-naphthyridin-3-yl)methyl]piperazin-1-yl}- N -methylpyridine-2-carboxamide (AZD5305): A PARP1-DNA Trapper with High Selectivity for PARP1 over PARP2 and Other PARPs.
Authors: Johannes, J.W. / Balazs, A. / Barratt, D. / Bista, M. / Chuba, M.D. / Cosulich, S. / Critchlow, S.E. / Degorce, S.L. / Di Fruscia, P. / Edmondson, S.D. / Embrey, K. / Fawell, S. / Ghosh, A. ...Authors: Johannes, J.W. / Balazs, A. / Barratt, D. / Bista, M. / Chuba, M.D. / Cosulich, S. / Critchlow, S.E. / Degorce, S.L. / Di Fruscia, P. / Edmondson, S.D. / Embrey, K. / Fawell, S. / Ghosh, A. / Gill, S.J. / Gunnarsson, A. / Hande, S.M. / Heightman, T.D. / Hemsley, P. / Illuzzi, G. / Lane, J. / Larner, C. / Leo, E. / Liu, L. / Madin, A. / Martin, S. / McWilliams, L. / O'Connor, M.J. / Orme, J.P. / Pachl, F. / Packer, M.J. / Pei, X. / Pike, A. / Schimpl, M. / She, H. / Staniszewska, A.D. / Talbot, V. / Underwood, E. / Varnes, J.G. / Xue, L. / Yao, T. / Zhang, K. / Zhang, A.X. / Zheng, X.
History
DepositionMay 25, 2021Deposition site: PDBE / Processing site: PDBE
Revision 1.0Sep 15, 2021Provider: repository / Type: Initial release
Revision 1.1Oct 13, 2021Group: Data collection / Database references
Category: citation / citation_author ...citation / citation_author / diffrn_source / pdbx_database_proc
Item: _citation.journal_abbrev / _citation.journal_id_CSD ..._citation.journal_abbrev / _citation.journal_id_CSD / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _diffrn_source.pdbx_synchrotron_site
Revision 1.2Oct 27, 2021Group: Data collection / Database references / Category: citation / citation_author / pdbx_database_proc
Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _citation_author.identifier_ORCID
Revision 1.3May 1, 2024Group: Data collection / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / diffrn_source / pdbx_initial_refinement_model
Item: _diffrn_source.pdbx_synchrotron_site

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Poly [ADP-ribose] polymerase 1
B: Poly [ADP-ribose] polymerase 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)79,6296
Polymers78,6262
Non-polymers1,0034
Water8,431468
1
A: Poly [ADP-ribose] polymerase 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)39,8143
Polymers39,3131
Non-polymers5022
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
2
B: Poly [ADP-ribose] polymerase 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)39,8143
Polymers39,3131
Non-polymers5022
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Unit cell
Length a, b, c (Å)48.573, 92.621, 164.312
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number19
Space group name H-MP212121

-
Components

#1: Protein Poly [ADP-ribose] polymerase 1 / PARP-1 / ADP-ribosyltransferase diphtheria toxin-like 1 / ARTD1 / DNA ADP-ribosyltransferase PARP1 ...PARP-1 / ADP-ribosyltransferase diphtheria toxin-like 1 / ARTD1 / DNA ADP-ribosyltransferase PARP1 / NAD(+) ADP-ribosyltransferase 1 / ADPRT 1 / Poly[ADP-ribose] synthase 1 / Protein poly-ADP-ribosyltransferase PARP1


Mass: 39312.934 Da / Num. of mol.: 2 / Fragment: catalytic domain (662-1101) / Mutation: V762A
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: PARP1, ADPRT, PPOL / Plasmid: pET24a / Production host: Escherichia coli (E. coli) / Strain (production host): BL21 Gold (DE3)
References: UniProt: P09874, NAD+ ADP-ribosyltransferase, Transferases; Glycosyltransferases; Pentosyltransferases
#2: Chemical ChemComp-VKQ / 5-[4-[(3-ethyl-2-oxidanylidene-1~{H}-quinolin-7-yl)methyl]piperazin-1-yl]-~{N}-methyl-pyridine-2-carboxamide


Mass: 405.493 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C23H27N5O2 / Feature type: SUBJECT OF INVESTIGATION
#3: Chemical ChemComp-SO4 / SULFATE ION


Mass: 96.063 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: SO4
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 468 / 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: 2.35 Å3/Da / Density % sol: 47.67 %
Crystal growTemperature: 293 K / Method: vapor diffusion / pH: 9.5 / Details: 2.5 M ammonium sulfate, 0.1 M Tris pH 8.5

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: Diamond / Beamline: I03 / Wavelength: 0.97625 Å
DetectorType: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Oct 5, 2018
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.97625 Å / Relative weight: 1
ReflectionResolution: 1.85→82.16 Å / Num. obs: 50296 / % possible obs: 93.3 % / Redundancy: 6.5 % / Biso Wilson estimate: 27.2 Å2 / CC1/2: 0.997 / Rmerge(I) obs: 0.143 / Net I/σ(I): 9.2
Reflection shellResolution: 1.85→1.989 Å / Rmerge(I) obs: 1.354 / Mean I/σ(I) obs: 1.5 / Num. unique obs: 2516 / CC1/2: 0.482

-
Processing

Software
NameVersionClassification
BUSTER2.11.8 (24-FEB-2021)refinement
XDSdata reduction
PDB_EXTRACT3.25data extraction
STARANISOdata scaling
AMoREphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: internal model

Resolution: 1.853→82.16 Å / Cor.coef. Fo:Fc: 0.939 / Cor.coef. Fo:Fc free: 0.921 / SU R Cruickshank DPI: 0.204 / Cross valid method: THROUGHOUT / σ(F): 0 / SU R Blow DPI: 0.216 / SU Rfree Blow DPI: 0.172 / SU Rfree Cruickshank DPI: 0.169
RfactorNum. reflection% reflectionSelection details
Rfree0.2438 2471 4.91 %RANDOM
Rwork0.2131 ---
obs0.2146 50296 78.7 %-
Displacement parametersBiso max: 81.87 Å2 / Biso mean: 33.37 Å2 / Biso min: 11.87 Å2
Baniso -1Baniso -2Baniso -3
1-3.187 Å20 Å20 Å2
2---0.1385 Å20 Å2
3----3.0485 Å2
Refine analyzeLuzzati coordinate error obs: 0.27 Å
Refinement stepCycle: final / Resolution: 1.853→82.16 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms5468 0 70 468 6006
Biso mean--24.2 36.73 -
Num. residues----700
Refine LS restraints
Refine-IDTypeNumberRestraint functionWeightDev ideal
X-RAY DIFFRACTIONt_dihedral_angle_d2021SINUSOIDAL2
X-RAY DIFFRACTIONt_trig_c_planes
X-RAY DIFFRACTIONt_gen_planes939HARMONIC5
X-RAY DIFFRACTIONt_it5646HARMONIC10
X-RAY DIFFRACTIONt_nbd
X-RAY DIFFRACTIONt_improper_torsion
X-RAY DIFFRACTIONt_pseud_angle
X-RAY DIFFRACTIONt_chiral_improper_torsion732SEMIHARMONIC5
X-RAY DIFFRACTIONt_sum_occupancies
X-RAY DIFFRACTIONt_utility_distance
X-RAY DIFFRACTIONt_utility_angle
X-RAY DIFFRACTIONt_utility_torsion
X-RAY DIFFRACTIONt_ideal_dist_contact4880SEMIHARMONIC4
X-RAY DIFFRACTIONt_bond_d5646HARMONIC20.008
X-RAY DIFFRACTIONt_angle_deg7631HARMONIC20.97
X-RAY DIFFRACTIONt_omega_torsion3.33
X-RAY DIFFRACTIONt_other_torsion16.46
LS refinement shellResolution: 1.853→1.94 Å / Rfactor Rfree error: 0
RfactorNum. reflection% reflection
Rfree0.2667 37 3.68 %
Rwork0.308 969 -
obs--12.34 %
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)
10.57520.0535-0.02370.3561-0.16840.3916-0.0519-0.00290.0299-0.01690.01930.00310.0235-0.01450.03260.0150.0247-0.0291-0.0173-0.0199-0.06329.585443.37715.0709
20.369-0.08590.42180.3319-0.73643.27580.0093-0.0526-0.10210.00770.1412-0.0255-0.0375-0.1712-0.1504-0.01760.0343-0.0149-0.030.0306-0.106430.677526.23438.1256
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection detailsAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1{ A|* }A662 - 1011
2X-RAY DIFFRACTION2{ B|* }B662 - 1011

+
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