2L30

Human PARP-1 zinc finger 1


Experimental Data Snapshot

  • Method: SOLUTION NMR
  • Conformers Calculated: 50 
  • Conformers Submitted: 30 
  • Selection Criteria: structures with the lowest energy 

wwPDB Validation   3D Report Full Report


This is version 1.2 of the entry. See complete history


Literature

The DNA-binding domain of human PARP-1 interacts with DNA single-strand breaks as a monomer through its second zinc finger.

Eustermann, S.Videler, H.Yang, J.C.Cole, P.T.Gruszka, D.Veprintsev, D.Neuhaus, D.

(2011) J Mol Biol 407: 149-170

  • DOI: https://doi.org/10.1016/j.jmb.2011.01.034
  • Primary Citation of Related Structures:  
    2L30, 2L31

  • PubMed Abstract: 

    Poly(ADP-ribose)polymerase-1 (PARP-1) is a highly abundant chromatin-associated enzyme present in all higher eukaryotic cell nuclei, where it plays key roles in the maintenance of genomic integrity, chromatin remodeling and transcriptional control. It binds to DNA single- and double-strand breaks through an N-terminal region containing two zinc fingers, F1 and F2, following which its C-terminal catalytic domain becomes activated via an unknown mechanism, causing formation and addition of polyadenosine-ribose (PAR) to acceptor proteins including PARP-1 itself. Here, we report a biophysical and structural characterization of the F1 and F2 fingers of human PARP-1, both as independent fragments and in the context of the 24-kDa DNA-binding domain (F1+F2). We show that the fingers are structurally independent in the absence of DNA and share a highly similar structural fold and dynamics. The F1+F2 fragment recognizes DNA single-strand breaks as a monomer and in a single orientation. Using a combination of NMR spectroscopy and other biophysical techniques, we show that recognition is primarily achieved by F2, which binds the DNA in an essentially identical manner whether present in isolation or in the two-finger fragment. F2 interacts much more strongly with nicked or gapped DNA ligands than does F1, and we present a mutational study that suggests origins of this difference. Our data suggest that different DNA lesions are recognized by the DNA-binding domain of PARP-1 in a highly similar conformation, helping to rationalize how the full-length protein participates in multiple steps of DNA single-strand breakage and base excision repair.


  • Organizational Affiliation

    MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 0QH, UK.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Poly [ADP-ribose] polymerase 1108Homo sapiensMutation(s): 0 
Gene Names: PARP1ADPRTPPOL
EC: 2.4.2.30
UniProt & NIH Common Fund Data Resources
Find proteins for P09874 (Homo sapiens)
Explore P09874 
Go to UniProtKB:  P09874
PHAROS:  P09874
GTEx:  ENSG00000143799 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP09874
Sequence Annotations
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  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
ZN
Query on ZN

Download Ideal Coordinates CCD File 
B [auth A]ZINC ION
Zn
PTFCDOFLOPIGGS-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: SOLUTION NMR
  • Conformers Calculated: 50 
  • Conformers Submitted: 30 
  • Selection Criteria: structures with the lowest energy 

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2011-02-02
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2019-12-25
    Changes: Data collection, Database references