spacer
spacer
Go to PDB code: 
protein ligands links
Transferase PDB id
4pax
Jmol
Contents
Protein chain
350 a.a. *
Ligands
NU1
Waters ×54
* Residue conservation analysis
PDB id:
4pax
Name: Transferase
Title: The catalytic fragment of poly(adp-ribose) polymerase complexed with 8-hydroxy-2-methyl-3-hydro-quinazolin-4-one
Structure: Poly(adp-ribose) polymerase. Chain: a. Fragment: catalytic fragment. Synonym: parp-cf, poly(adp-ribose) transferase, poly (adp- ribose) synthetase. Engineered: yes
Source: Gallus gallus. Chicken. Organism_taxid: 9031. Cell_line: sf9. Organelle: nucleus. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108. Expression_system_cell_line: sf9.
Resolution:
2.80Å     R-factor:   0.167    
Authors: A.Ruf,G.E.Schulz
Key ref:
A.Ruf et al. (1998). Inhibitor and NAD+ binding to poly(ADP-ribose) polymerase as derived from crystal structures and homology modeling. Biochemistry, 37, 3893-3900. PubMed id: 9521710 DOI: 10.1021/bi972383s
Date:
25-Nov-97     Release date:   27-May-98    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P26446  (PARP1_CHICK) -  Poly [ADP-ribose] polymerase 1
Seq:
Struc: 		 
Seq:
Struc: 		1011 a.a.
350 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.2.4.2.30  - NAD(+) ADP-ribosyltransferase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

      Pathway: 		NAD+ ADP-ribosyltransferase
      Reaction: NAD+ + (ADP-D-ribosyl)(n)-acceptor = nicotinamide + (ADP-D- ribosyl)(n+1)-acceptor
NAD(+)
 + (ADP-D-ribosyl)(n)-acceptor
 =
nicotinamide
Bound ligand (Het Group name = NU1)
matches with 69.00% similarity 		+ (ADP-D- ribosyl)(n+1)-acceptor
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     protein amino acid ADP-ribosylation   1 term 
  Biochemical function     NAD+ ADP-ribosyltransferase activity     1 term  

 

 
    Added reference    
 
 
DOI no: 10.1021/bi972383s Biochemistry 37:3893-3900 (1998)
PubMed id: 9521710  
 
 
Inhibitor and NAD+ binding to poly(ADP-ribose) polymerase as derived from crystal structures and homology modeling.
A.Ruf, G.de Murcia, G.E.Schulz.
 
  ABSTRACT  
 
Inhibitors of poly(ADP-ribose) polymerase (PARP, EC 2.4.2.30) are of clinical interest because they have potential for improving radiation therapy and chemotherapy of cancer. The refined binding structures of four such inhibitors are reported together with the refined structure of the unligated catalytic fragment of the enzyme. Following their design, all inhibitors bind at the position of the nicotinamide moiety of the substrate NAD+. The observed binding mode suggests inhibitor improvements that avoid other NAD(+)-binding enzymes. Because the binding pocket of NAD+ has been strongly conserved during evolution, the homology with ADP-ribosylating bacterial toxins could be used to extend the bound nicotinamide, which is marked by the inhibitors, to the full NAD+ molecule.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
20645701 F.Heitz, P.Harter, N.Ewald-Riegler, M.Papsdorf, S.Kommoss, and A.du Bois (2010).
Poly(ADP-ribosyl)ation polymerases: mechanism and new target of anticancer therapy.
  Expert Rev Anticancer Ther, 10, 1125-1136.  
20525793 S.Messner, M.Altmeyer, H.Zhao, A.Pozivil, B.Roschitzki, P.Gehrig, D.Rutishauser, D.Huang, A.Caflisch, and M.O.Hottiger (2010).
PARP1 ADP-ribosylates lysine residues of the core histone tails.
  Nucleic Acids Res, 38, 6350-6362.  
19715739 L.M.Giammona, S.Panuganti, J.M.Kemper, P.A.Apostolidis, S.Lindsey, E.T.Papoutsakis, and W.M.Miller (2009).
Mechanistic studies on the effects of nicotinamide on megakaryocytic polyploidization and the roles of NAD+ levels and SIRT inhibition.
  Exp Hematol, 37, 1340.  
  20157531 M.Altmeyer, and M.O.Hottiger (2009).
Poly(ADP-ribose) polymerase 1 at the crossroad of metabolic stress and inflammation in aging.
  Aging (Albany NY), 1, 458-469.  
19339067 R.L.van Montfort, and P.Workman (2009).
Structure-based design of molecular cancer therapeutics.
  Trends Biotechnol, 27, 315-328.  
18599483 B.Buelow, Y.Song, and A.M.Scharenberg (2008).
The Poly(ADP-ribose) Polymerase PARP-1 Is Required for Oxidative Stress-induced TRPM2 Activation in Lymphocytes.
  J Biol Chem, 283, 24571-24583.  
18225958 J.A.Kerns, M.Emerman, and H.S.Malik (2008).
Positive selection and increased antiviral activity associated with the PARP-containing isoform of human zinc-finger antiviral protein.
  PLoS Genet, 4, e21.  
17113833 J.K.Horton, and S.H.Wilson (2007).
Hypersensitivity phenotypes associated with genetic and synthetic inhibitor-induced base excision repair deficiency.
  DNA Repair (Amst), 6, 530-543.  
16892389 D.Bellocchi, G.Costantino, R.Pellicciari, N.Re, A.Marrone, and C.Coletti (2006).
Poly(ADP-ribose)-polymerase-catalyzed hydrolysis of NAD+: QM/MM simulation of the enzyme reaction.
  ChemMedChem, 1, 533-539.  
17178241 P.Massullo, A.Sumoza-Toledo, H.Bhagat, and S.Partida-Sánchez (2006).
TRPM channels, calcium and redox sensors during innate immune responses.
  Semin Cell Dev Biol, 17, 654-666.  
15561722 A.L.Perraud, C.L.Takanishi, B.Shen, S.Kang, M.K.Smith, C.Schmitz, H.M.Knowles, D.Ferraris, W.Li, J.Zhang, B.L.Stoddard, and A.M.Scharenberg (2005).
Accumulation of free ADP-ribose from mitochondria mediates oxidative stress-induced gating of TRPM2 cation channels.
  J Biol Chem, 280, 6138-6148.  
16001276 A.M.Scharenberg (2005).
TRPM2 and TRPM7: channel/enzyme fusions to generate novel intracellular sensors.
  Pflugers Arch, 451, 220-227.  
15670923 D.Bellocchi, A.Macchiarulo, G.Costantino, and R.Pellicciari (2005).
Docking studies on PARP-1 inhibitors: insights into the role of a binding pocket water molecule.
  Bioorg Med Chem, 13, 1151-1157.  
15701627 J.K.Horton, D.F.Stefanick, J.M.Naron, P.S.Kedar, and S.H.Wilson (2005).
Poly(ADP-ribose) polymerase activity prevents signaling pathways for cell cycle arrest after DNA methylating agent exposure.
  J Biol Chem, 280, 15773-15785.  
15864271 P.Jagtap, and C.Szabó (2005).
Poly(ADP-ribose) polymerase and the therapeutic effects of its inhibitors.
  Nat Rev Drug Discov, 4, 421-440.  
16061477 R.C.Aguiar, K.Takeyama, C.He, K.Kreinbrink, and M.A.Shipp (2005).
B-aggressive lymphoma family proteins have unique domains that modulate transcription and exhibit poly(ADP-ribose) polymerase activity.
  J Biol Chem, 280, 33756-33765.  
14739238 A.W.Oliver, J.C.Amé, S.M.Roe, V.Good, G.de Murcia, and L.H.Pearl (2004).
Crystal structure of the catalytic fragment of murine poly(ADP-ribose) polymerase-2.
  Nucleic Acids Res, 32, 456-464.
PDB code: 1gs0
  11246023 S.Smith (2001).
The world according to PARP.
  Trends Biochem Sci, 26, 174-179.  
10809783 F.R.Sallmann, M.D.Vodenicharov, Z.Q.Wang, and G.G.Poirier (2000).
Characterization of sPARP-1. An alternative product of PARP-1 gene with poly(ADP-ribose) polymerase activity independent of DNA strand breaks.
  J Biol Chem, 275, 15504-15511.  
10477748 V.A.Kickhoefer, A.C.Siva, N.L.Kedersha, E.M.Inman, C.Ruland, M.Streuli, and L.H.Rome (1999).
The 193-kD vault protein, VPARP, is a novel poly(ADP-ribose) polymerase.
  J Cell Biol, 146, 917-928.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.