Home LiteratureArticle Details
PMID: 8755499 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Structure of the catalytic fragment of poly(AD-ribose) polymerase from chicken.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 93 ·No. 15 ·1996-07-23 ·Pages 7481-5

Ruf A, Mennissier de Murcia J, de Murcia G, Schulz GE

Abstract

The crystal structures of the catalytic fragment of chicken poly(ADP-ribose) polymerase [NAD+ ADP-ribosyltransferase; NAD+:poly(adenosine-diphosphate-D-ribosyl)-acceptor ADP-D-ribosyltransferase, EC 2.4.2.30] with and without a nicotinamide-analogue inhibitor have been elucidated. Because this enzyme is involved in the regulation of DNA repair, its inhibitors are of interest for cancer therapy. The inhibitor shows the nicotinamide site and also suggests the adenosine site. The enzyme is structurally related to bacterial ADP-ribosylating toxins but contains an additional alpha-helical domain that is suggested to relay the activation signal issued on binding to damaged DNA.

MeSH Terms
Animals Binding Sites Cell Line Chickens Crystallography, X-Ray DNA Damage DNA Repair Humans Models, Molecular Molecular Sequence Data NAD/metabolism Peptide Fragments/biosynthesis,chemistry Poly(ADP-ribose) Polymerases/biosynthesis,chemistry Protein Structure, Secondary Recombinant Proteins/biosynthesis,chemistry Spodoptera Transfection
Chemicals
Peptide Fragments Recombinant Proteins NAD Poly(ADP-ribose) Polymerases
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Ruf A
Institut für Organische Chemie und Biochemie, Freiburg im Breisgau, Germany.
Mennissier de Murcia J
de Murcia G
Schulz G E
References (29)
29 references, click to expand
  1. Inhibitors of poly(ADP-ribose) synthesis enhance X-ray killing of log-phase Chinese hamster cells.
    Radiat Res. 1984 Mar;97(3):546-55 PMID: 6328564
  2. Crystal structure of diphtheria toxin bound to nicotinamide adenine dinucleotide.
    Biochemistry. 1996 Jan 30;35(4):1137-49 PMID: 8573568
  3. Computer modelling of the NAD binding site of ADP-ribosylating toxins: active-site structure and mechanism of NAD binding.
    Mol Microbiol. 1991 Jan;5(1):23-31 PMID: 1901617
  4. Improved methods for building protein models in electron density maps and the location of errors in these models.
    Acta Crystallogr A. 1991 Mar 1;47 ( Pt 2):110-9 PMID: 2025413
  5. Effect of PD 128763, a new potent inhibitor of poly(ADP-ribose) polymerase, on X-ray-induced cellular recovery processes in Chinese hamster V79 cells.
    Radiat Res. 1991 Jun;126(3):367-71 PMID: 1903547
  6. Dihydroisoquinolinones: the design and synthesis of a new series of potent inhibitors of poly(ADP-ribose) polymerase.
    Anticancer Drug Des. 1991 May;6(2):107-17 PMID: 1903948
  7. Enhancement of alkylating agent activity in vitro by PD 128763, a potent poly(ADP-ribose) synthetase inhibitor.
    Int J Radiat Oncol Biol Phys. 1992;22(3):619-21 PMID: 1531221
  8. Subunit assembly and active site location in the structure of glutamate dehydrogenase.
    Proteins. 1992 Jan;12(1):75-86 PMID: 1553382
  9. The crystal structure of diphtheria toxin.
    Nature. 1992 May 21;357(6375):216-22 PMID: 1589020
  10. NAD(+)-dependent repair of damaged DNA by human cell extracts.
    J Biol Chem. 1993 Mar 15;268(8):5480-7 PMID: 7680646
  11. Identification of potential active-site residues in the human poly(ADP-ribose) polymerase.
    J Biol Chem. 1993 Apr 25;268(12):8529-35 PMID: 8473297
  12. Refined structure of Escherichia coli heat-labile enterotoxin, a close relative of cholera toxin.
    J Mol Biol. 1993 Apr 5;230(3):890-918 PMID: 8478941
  13. Overproduction of the poly(ADP-ribose) polymerase DNA-binding domain blocks alkylation-induced DNA repair synthesis in mammalian cells.
    EMBO J. 1993 May;12(5):2109-17 PMID: 8491199
  14. The carboxyl-terminal domain of human poly(ADP-ribose) polymerase. Overproduction in Escherichia coli, large scale purification, and characterization.
    J Biol Chem. 1993 Jun 25;268(18):13454-61 PMID: 8390463
  15. Molecular and biochemical features of poly (ADP-ribose) metabolism.
    Mol Cell Biochem. 1993 May 26;122(2):171-93 PMID: 8232248
  16. Poly(ADP-ribose) polymerase: a molecular nick-sensor.
    Trends Biochem Sci. 1994 Apr;19(4):172-6 PMID: 8016868
  17. The crystal structure of pertussis toxin.
    Structure. 1994 Jan 15;2(1):45-57 PMID: 8075982
  18. Crystallization and X-ray crystallographic analysis of recombinant chicken poly(ADP-ribose) polymerase catalytic domain produced in Sf9 insect cells.
    J Mol Biol. 1994 Nov 18;244(1):114-6 PMID: 7966315
  19. Structure of the isolated catalytic domain of diphtheria toxin.
    Biochemistry. 1995 Jan 24;34(3):773-81 PMID: 7827036
  20. Common features of the NAD-binding and catalytic site of ADP-ribosylating toxins.
    Mol Microbiol. 1994 Oct;14(1):41-50 PMID: 7830559
  21. Refined structure of dimeric diphtheria toxin at 2.0 A resolution.
    Protein Sci. 1994 Sep;3(9):1444-63 PMID: 7833807
  22. Role of glutamic acid 988 of human poly-ADP-ribose polymerase in polymer formation. Evidence for active site similarities to the ADP-ribosylating toxins.
    J Biol Chem. 1995 Feb 17;270(7):3247-54 PMID: 7852410
  23. Common structure of the catalytic sites of mammalian and bacterial toxin ADP-ribosyltransferases.
    Mol Cell Biochem. 1994 Sep;138(1-2):177-81 PMID: 7898462
  24. A dominant-negative mutant of human poly(ADP-ribose) polymerase affects cell recovery, apoptosis, and sister chromatid exchange following DNA damage.
    Proc Natl Acad Sci U S A. 1995 May 23;92(11):4753-7 PMID: 7761396
  25. The three-dimensional crystal structure of cholera toxin.
    J Mol Biol. 1995 Aug 25;251(4):563-73 PMID: 7658473
  26. The role of inhibitors of poly(ADP-ribose) polymerase as resistance-modifying agents in cancer therapy.
    Biochimie. 1995;77(6):408-22 PMID: 7578423
  27. Poly(ADP-ribose) polymerase: structure-function relationship.
    Biochimie. 1995;77(6):456-61 PMID: 7578429
  28. The crystal structure of Pseudomonas aeruginosa exotoxin domain III with nicotinamide and AMP: conformational differences with the intact exotoxin.
    Proc Natl Acad Sci U S A. 1995 Sep 26;92(20):9308-12 PMID: 7568123
  29. Structure of exotoxin A of Pseudomonas aeruginosa at 3.0-Angstrom resolution.
    Proc Natl Acad Sci U S A. 1986 Mar;83(5):1320-4 PMID: 3006045
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.93.15.7481
Published
1996-07-23
Pages
7481-5
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC38770
Subset
IM
Databases
PDB
1PAW, 1PAX
External Links
PubMed source DOI: 10.1073/pnas.93.15.7481 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2