[English] 日本語
Yorodumi
- PDB-4zzy: Structure of human PARP2 catalytic domain bound to an isoindolino... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 4zzy
TitleStructure of human PARP2 catalytic domain bound to an isoindolinone inhibitor
ComponentsPOLY [ADP-RIBOSE] POLYMERASE 2
KeywordsTRANSFERASE
Function / homology
Function and homology information


hippocampal neuron apoptotic process / response to oxygen-glucose deprivation / poly-ADP-D-ribose binding / positive regulation of cell growth involved in cardiac muscle cell development / poly-ADP-D-ribose modification-dependent protein binding / NAD+-protein-serine ADP-ribosyltransferase activity / NAD DNA ADP-ribosyltransferase activity / NAD+-protein-aspartate ADP-ribosyltransferase activity / NAD+-protein-glutamate ADP-ribosyltransferase activity / DNA ADP-ribosylation ...hippocampal neuron apoptotic process / response to oxygen-glucose deprivation / poly-ADP-D-ribose binding / positive regulation of cell growth involved in cardiac muscle cell development / poly-ADP-D-ribose modification-dependent protein binding / NAD+-protein-serine ADP-ribosyltransferase activity / NAD DNA ADP-ribosyltransferase activity / NAD+-protein-aspartate ADP-ribosyltransferase activity / NAD+-protein-glutamate ADP-ribosyltransferase activity / DNA ADP-ribosylation / HDR through MMEJ (alt-NHEJ) / NAD+ ADP-ribosyltransferase / DNA repair-dependent chromatin remodeling / protein auto-ADP-ribosylation / protein poly-ADP-ribosylation / NAD+-protein ADP-ribosyltransferase activity / site of DNA damage / decidualization / NAD+-protein poly-ADP-ribosyltransferase activity / Transferases; Glycosyltransferases; Pentosyltransferases / nucleosome binding / POLB-Dependent Long Patch Base Excision Repair / extrinsic apoptotic signaling pathway / nucleotidyltransferase activity / DNA Damage Recognition in GG-NER / base-excision repair / Dual Incision in GG-NER / Formation of Incision Complex in GG-NER / double-strand break repair / damaged DNA binding / DNA repair / DNA damage response / chromatin binding / nucleolus / nucleoplasm / nucleus
Similarity search - Function
Poly(ADP-ribose) polymerase, regulatory domain / Poly(ADP-ribose) Polymerase; domain 1 / : / 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 / Poly(ADP-ribose) Polymerase; domain 1 / : / 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 / Poly(ADP-ribose) polymerase catalytic domain / Poly(ADP-ribose) polymerase, catalytic domain / PARP catalytic domain profile. / Alpha-Beta Complex / Up-down Bundle / Mainly Alpha / Alpha Beta
Similarity search - Domain/homology
Chem-D7N / Poly [ADP-ribose] polymerase 2
Similarity search - Component
Biological speciesHOMO SAPIENS (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.2 Å
AuthorsCasale, E. / Fasolini, M. / Papeo, G. / Posteri, H. / Borghi, D. / Busel, A.A. / Caprera, F. / Ciomei, M. / Cirla, A. / Corti, E. ...Casale, E. / Fasolini, M. / Papeo, G. / Posteri, H. / Borghi, D. / Busel, A.A. / Caprera, F. / Ciomei, M. / Cirla, A. / Corti, E. / DAnello, M. / Fasolini, M. / Felder, E.R. / Forte, B. / Galvani, A. / Isacchi, A. / Khvat, A. / Krasavin, M.Y. / Lupi, R. / Orsini, P. / Perego, R. / Pesenti, E. / Pezzetta, D. / Rainoldi, S. / RiccardiSirtori, F. / Scolaro, A. / Sola, F. / Zuccotto, F. / Donati, D. / Montagnoli, A.
CitationJournal: J.Med.Chem. / Year: 2015
Title: Discovery of 2-[1-(4,4-Difluorocyclohexyl)Piperidin-4-Yl]-6-Fluoro-3-Oxo-2,3-Dihydro-1H-Isoindole-4-Carboxamide (Nms-P118): A Potent, Orally Available and Highly Selective Parp- 1 Inhibitor for Cancer Therapy.
Authors: Papeo, G.M.E. / Posteri, H. / Borghi, D. / Busel, A.A. / Caprera, F. / Casale, E. / Ciomei, M. / Cirla, A. / Corti, E. / D'Anello, M. / Fasolini, M. / Forte, B. / Galvani, A. / Isacchi, A. / ...Authors: Papeo, G.M.E. / Posteri, H. / Borghi, D. / Busel, A.A. / Caprera, F. / Casale, E. / Ciomei, M. / Cirla, A. / Corti, E. / D'Anello, M. / Fasolini, M. / Forte, B. / Galvani, A. / Isacchi, A. / Khvat, A. / Krasavin, M.Y. / Lupi, R. / Orsini, P. / Perego, R. / Pesenti, E. / Pezzetta, D. / Rainoldi, S. / Riccardi-Sirtori, F. / Scolaro, A. / Sola, F. / Zuccotto, F. / Felder, E.R. / Donati, D. / Montagnoli, A.
History
DepositionApr 15, 2015Deposition site: PDBE / Processing site: PDBE
Revision 1.0Aug 12, 2015Provider: repository / Type: Initial release
Revision 1.1Sep 23, 2015Group: Database references
Revision 1.2Jan 10, 2024Group: Data collection / Database references ...Data collection / Database references / Derived calculations / Other / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_database_status / pdbx_initial_refinement_model / struct_site
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _pdbx_database_status.status_code_sf / _struct_site.pdbx_auth_asym_id / _struct_site.pdbx_auth_comp_id / _struct_site.pdbx_auth_seq_id

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: POLY [ADP-RIBOSE] POLYMERASE 2
hetero molecules


Theoretical massNumber of molelcules
Total (without water)41,4982
Polymers41,1021
Non-polymers3951
Water1,44180
1


  • Idetical with deposited unit
  • defined by software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)74.377, 74.377, 148.463
Angle α, β, γ (deg.)90.00, 90.00, 90.00
Int Tables number96
Space group name H-MP43212

-
Components

#1: Protein POLY [ADP-RIBOSE] POLYMERASE 2 / PARP-2 / HPARP-2 / ADP-RIBOSYLTRANSFERASE DIPHTHERIA TOXIN-LI KE 2 / ARTD2 / NAD(+) ADP- ...PARP-2 / HPARP-2 / ADP-RIBOSYLTRANSFERASE DIPHTHERIA TOXIN-LI KE 2 / ARTD2 / NAD(+) ADP-RIBOSYLTRANSFERASE 2 / ADPRT-2 / POLYADP-RIB OSE SYNTHASE 2 / PADPRT-2 / PARP-2 / HPARP-2 / ADP-RIBOSYLTRANSFERASE DIPHTHERIA TOXIN-LIKE 2 / ARTD2 / NAD(+) ADP-RIBOSYLTRANSFERASE 2 / A DPRT-2 / POLYADP- RIBOSE SYNTHASE 2 / PADPRT-2 / POLY ADP-RIBOSE POLY MERASE 2 / POLY ADP-RIBOSE POLYMERASE 2


Mass: 41102.309 Da / Num. of mol.: 1 / Fragment: CATALYTIC DOMAIN, UNP RESIDUES 223-583
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) HOMO SAPIENS (human) / Plasmid: PET28A / Production host: ESCHERICHIA COLI (E. coli) / Strain (production host): BL21 / References: UniProt: Q9UGN5, NAD+ ADP-ribosyltransferase
#2: Chemical ChemComp-D7N / 2-[1-(4,4-Difluorocyclohexyl)-piperidin-4-yl]-6-fluoro-3-oxo-2,3-dihydro-1H-isoindole-4-carboxamide


Mass: 395.419 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C20H24F3N3O2
#3: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 80 / Source method: isolated from a natural source / Formula: H2O
Sequence detailsGLY221 AND PRO222 ARE EXPRESSION TAG

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.54 Å3/Da / Density % sol: 51.2 % / Description: NONE
Crystal growDetails: 25% PEG4000, 0.2M MAGNESIUM CLORIDE, 0.1 M TRIS PH 8.5

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: ESRF / Beamline: ID23-1 / Wavelength: 1.07
DetectorType: DECTRIS PILATUS 6M / Detector: PIXEL
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.07 Å / Relative weight: 1
ReflectionResolution: 2.2→30 Å / Num. obs: 21921 / % possible obs: 99.8 % / Observed criterion σ(I): 0 / Redundancy: 7 % / Rmerge(I) obs: 0.08 / Net I/σ(I): 20.6
Reflection shellResolution: 2.2→2.32 Å / Rmerge(I) obs: 0.45 / Mean I/σ(I) obs: 6.5 / % possible all: 99.9

-
Processing

Software
NameVersionClassification
REFMAC5.6.0117refinement
MOSFLMdata reduction
SCALAdata scaling
MOLREPphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: PDB ENTRY 3KCZ

3kcz


Resolution: 2.2→66.5 Å / Cor.coef. Fo:Fc: 0.931 / Cor.coef. Fo:Fc free: 0.883 / SU B: 7.135 / SU ML: 0.179 / Cross valid method: THROUGHOUT / ESU R: 0.273 / ESU R Free: 0.235 / Stereochemistry target values: MAXIMUM LIKELIHOOD / Details: HYDROGENS HAVE BEEN USED IF PRESENT IN THE INPUT
RfactorNum. reflection% reflectionSelection details
Rfree0.28037 1122 5.1 %RANDOM
Rwork0.21618 ---
obs0.21945 20733 99.7 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK
Displacement parametersBiso mean: 26.354 Å2
Baniso -1Baniso -2Baniso -3
1--1.04 Å20 Å20 Å2
2---1.04 Å20 Å2
3---2.09 Å2
Refinement stepCycle: LAST / Resolution: 2.2→66.5 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2796 0 28 80 2904
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0160.022886
X-RAY DIFFRACTIONr_bond_other_d
X-RAY DIFFRACTIONr_angle_refined_deg1.8561.9883901
X-RAY DIFFRACTIONr_angle_other_deg
X-RAY DIFFRACTIONr_dihedral_angle_1_deg6.7675349
X-RAY DIFFRACTIONr_dihedral_angle_2_deg37.84724.462130
X-RAY DIFFRACTIONr_dihedral_angle_3_deg18.13815524
X-RAY DIFFRACTIONr_dihedral_angle_4_deg20.7571515
X-RAY DIFFRACTIONr_chiral_restr0.1150.2427
X-RAY DIFFRACTIONr_gen_planes_refined0.0090.0212152
X-RAY DIFFRACTIONr_gen_planes_other
X-RAY DIFFRACTIONr_nbd_refined
X-RAY DIFFRACTIONr_nbd_other
X-RAY DIFFRACTIONr_nbtor_refined
X-RAY DIFFRACTIONr_nbtor_other
X-RAY DIFFRACTIONr_xyhbond_nbd_refined
X-RAY DIFFRACTIONr_xyhbond_nbd_other
X-RAY DIFFRACTIONr_metal_ion_refined
X-RAY DIFFRACTIONr_metal_ion_other
X-RAY DIFFRACTIONr_symmetry_vdw_refined
X-RAY DIFFRACTIONr_symmetry_vdw_other
X-RAY DIFFRACTIONr_symmetry_hbond_refined
X-RAY DIFFRACTIONr_symmetry_hbond_other
X-RAY DIFFRACTIONr_symmetry_metal_ion_refined
X-RAY DIFFRACTIONr_symmetry_metal_ion_other
X-RAY DIFFRACTIONr_mcbond_it
X-RAY DIFFRACTIONr_mcbond_other
X-RAY DIFFRACTIONr_mcangle_it
X-RAY DIFFRACTIONr_mcangle_other
X-RAY DIFFRACTIONr_scbond_it
X-RAY DIFFRACTIONr_scbond_other
X-RAY DIFFRACTIONr_scangle_it
X-RAY DIFFRACTIONr_scangle_other
X-RAY DIFFRACTIONr_long_range_B_refined
X-RAY DIFFRACTIONr_long_range_B_other
X-RAY DIFFRACTIONr_rigid_bond_restr
X-RAY DIFFRACTIONr_sphericity_free
X-RAY DIFFRACTIONr_sphericity_bonded
LS refinement shellResolution: 2.2→2.257 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.396 83 -
Rwork0.308 1334 -
obs--99.86 %

+
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