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PDBsum entry 1a26

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Transferase PDB id
1a26
Jmol
Contents
Protein chain
351 a.a. *
Ligands
CNA
Waters ×90
* Residue conservation analysis
PDB id:
1a26
Name: Transferase
Title: The catalytic fragment of poly(adp-ribose) polymerase complexed with carba-NAD
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:
2.25Å     R-factor:   0.168     R-free:   0.236
Authors: A.Ruf,G.E.Schulz
Key ref:
A.Ruf et al. (1998). The mechanism of the elongation and branching reaction of poly(ADP-ribose) polymerase as derived from crystal structures and mutagenesis. J Mol Biol, 278, 57-65. PubMed id: 9571033 DOI: 10.1006/jmbi.1998.1673
Date:
16-Jan-98     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.
351 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(+)
Bound ligand (Het Group name = CNA)
matches with 61.00% similarity
+ (ADP-D-ribosyl)(n)-acceptor
= nicotinamide
+ (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 ADP-ribosylation   1 term 
  Biochemical function     NAD+ ADP-ribosyltransferase activity     1 term  

 

 
    Added reference    
 
 
DOI no: 10.1006/jmbi.1998.1673 J Mol Biol 278:57-65 (1998)
PubMed id: 9571033  
 
 
The mechanism of the elongation and branching reaction of poly(ADP-ribose) polymerase as derived from crystal structures and mutagenesis.
A.Ruf, V.Rolli, G.de Murcia, G.E.Schulz.
 
  ABSTRACT  
 
The binding site for the acceptor substrate poly(ADP-ribose) in the elongation reaction of the ADP-ribosyl transferase poly(ADP-ribose) polymerase (PARP) was detected by cocrystallizing the enzyme with an NAD+ analogue. The site was confirmed by mutagenesis studies. In conjunction with the binding site of the donor NAD+, the bound acceptor reveals the geometry of the elongation reaction. It shows in particular that the strictly conserved glutamate residue of all ADP-ribosylating enzymes (Glu988 of PARP) facilitates the reaction by polarizing both, donor and acceptor. Moreover, the binding properties of the acceptor site suggest a mechanism for the branching reaction, that also explains the dual specificity of this transferase for elongation and branching, which is unique among polymer-forming enzymes.
 
  Selected figure(s)  
 
Figure 2.
Figure 2. Covalent structure of the analogue carba-NAD [Slama and Simmons 1988]. The ring oxygen of the nicotinamide ribose is replaced by a methylene group, which prevents ADP-ribosyl transfer and hydrolysis of the nicotinamide moiety.
Figure 3.
Figure 3. ADP moiety of carba-NAD as bound to the acceptor site. (a), (3 F[obs]−2 F[calc]) electron density of the ADP moiety of bound carba-NAD contoured at 1.2 σ together with the final ADP model. This density was calculated after the first round of refinement when ADP was not yet included into F[calc] and is, therefore, unbiased. (b), Stereo view showing the environment of the ligand. Hydrogen bonds are depicted as dotted lines. The residue types can be read from Figure 5(b).
 
  The above figures are reprinted by permission from Elsevier: J Mol Biol (1998, 278, 57-65) copyright 1998.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
22713970 B.A.Gibson, and W.L.Kraus (2012).
New insights into the molecular and cellular functions of poly(ADP-ribose) and PARPs.
  Nat Rev Mol Cell Biol, 13, 411-424.  
20853319 A.Mangerich, and A.Bürkle (2011).
How to kill tumor cells with inhibitors of poly(ADP-ribosyl)ation.
  Int J Cancer, 128, 251-265.  
20106667 M.O.Hottiger, P.O.Hassa, B.Lüscher, H.Schüler, and F.Koch-Nolte (2010).
Toward a unified nomenclature for mammalian ADP-ribosyltransferases.
  Trends Biochem Sci, 35, 208-219.  
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.  
18851833 H.Kleine, E.Poreba, K.Lesniewicz, P.O.Hassa, M.O.Hottiger, D.W.Litchfield, B.H.Shilton, and B.Lüscher (2008).
Substrate-assisted catalysis by PARP10 limits its activity to mono-ADP-ribosylation.
  Mol Cell, 32, 57-69.  
18349144 J.Baysarowich, K.Koteva, D.W.Hughes, L.Ejim, E.Griffiths, K.Zhang, M.Junop, and G.D.Wright (2008).
Rifamycin antibiotic resistance by ADP-ribosylation: Structure and diversity of Arr.
  Proc Natl Acad Sci U S A, 105, 4886-4891.
PDB code: 2hw2
18644123 S.S.Haenni, M.Altmeyer, P.O.Hassa, T.Valovka, M.Fey, and M.O.Hottiger (2008).
Importin alpha binding and nuclear localization of PARP-2 is dependent on lysine 36, which is located within a predicted classical NLS.
  BMC Cell Biol, 9, 39.  
18436469 S.S.Haenni, P.O.Hassa, M.Altmeyer, M.Fey, R.Imhof, and M.O.Hottiger (2008).
Identification of lysines 36 and 37 of PARP-2 as targets for acetylation and auto-ADP-ribosylation.
  Int J Biochem Cell Biol, 40, 2274-2283.  
18019526 H.Lin (2007).
Nicotinamide adenine dinucleotide: beyond a redox coenzyme.
  Org Biomol Chem, 5, 2541-2554.  
17521358 K.K.Raju, H.S.Misra, and A.Sharma (2007).
Xanthomonas caspase displays an inherent PARP-like activity.
  FEMS Microbiol Lett, 272, 259-268.  
17478423 S.Goenka, S.H.Cho, and M.Boothby (2007).
Collaborator of Stat6 (CoaSt6)-associated poly(ADP-ribose) polymerase activity modulates Stat6-dependent gene transcription.
  J Biol Chem, 282, 18732-18739.  
16931513 A.R.Morrison, J.Moss, L.A.Stevens, J.E.Evans, C.Farrell, E.Merithew, D.G.Lambright, D.L.Greiner, J.P.Mordes, A.A.Rossini, and R.Bortell (2006).
ART2, a T cell surface mono-ADP-ribosyltransferase, generates extracellular poly(ADP-ribose).
  J Biol Chem, 281, 33363-33372.  
16959969 P.O.Hassa, S.S.Haenni, M.Elser, and M.O.Hottiger (2006).
Nuclear ADP-ribosylation reactions in mammalian cells: where are we today and where are we going?
  Microbiol Mol Biol Rev, 70, 789-829.  
16829982 V.Schreiber, F.Dantzer, J.C.Ame, and G.de Murcia (2006).
Poly(ADP-ribose): novel functions for an old molecule.
  Nat Rev Mol Cell Biol, 7, 517-528.  
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.  
15902274 G.I.Karras, G.Kustatscher, H.R.Buhecha, M.D.Allen, C.Pugieux, F.Sait, M.Bycroft, and A.G.Ladurner (2005).
The macro domain is an ADP-ribose binding module.
  EMBO J, 24, 1911-1920.
PDB codes: 2bfq 2bfr
16202152 H.Otto, P.A.Reche, F.Bazan, K.Dittmar, F.Haag, and F.Koch-Nolte (2005).
In silico characterization of the family of PARP-like poly(ADP-ribosyl)transferases (pARTs).
  BMC Genomics, 6, 139.  
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
12077446 C.Mueller-Dieckmann, T.Scheuermann, K.Wursthorn, J.Schröder, F.Haag, G.E.Schulz, and F.Koch-Nolte (2002).
Expression, purification, crystallization and preliminary X-ray analysis of rat ecto-ADP-ribosyltransferase 2 (ART2.2).
  Acta Crystallogr D Biol Crystallogr, 58, 1211-1213.  
11722768 E.Babiychuk, M.Van Montagu, and S.Kushnir (2001).
N-terminal domains of plant poly(ADP-ribose) polymerases define their association with mitotic chromosomes.
  Plant J, 28, 245-255.  
10972829 H.Otto, D.Tezcan-Merdol, R.Girisch, F.Haag, M.Rhen, and F.Koch-Nolte (2000).
The spvB gene-product of the Salmonella enterica virulence plasmid is a mono(ADP-ribosyl)transferase.
  Mol Microbiol, 37, 1106-1115.  
10364231 J.C.Amé, V.Rolli, V.Schreiber, C.Niedergang, F.Apiou, P.Decker, S.Muller, T.Höger, J.Ménissier-de Murcia, and G.de Murcia (1999).
PARP-2, A novel mammalian DNA damage-dependent poly(ADP-ribose) polymerase.
  J Biol Chem, 274, 17860-17868.  
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.