Tags

Type your tag names separated by a space and hit enter

Structural basis for inhibitor specificity in human poly(ADP-ribose) polymerase-3.
J Med Chem. 2009 May 14; 52(9):3108-11.JM

Abstract

Poly(ADP-ribose) polymerases (PARPs) activate DNA repair mechanisms upon stress- and cytotoxin-induced DNA damage, and inhibition of PARP activity is a lead in cancer drug therapy. We present a structural and functional analysis of the PARP domain of human PARP-3 in complex with several inhibitors. Of these, KU0058948 is the strongest inhibitor of PARP-3 activity. The presented crystal structures highlight key features for potent inhibitor binding and suggest routes for creating isoenzyme-specific PARP inhibitors.

Links

Publisher Full Text (DOI)

Authors+Show Affiliations

Lehtiö L
Structural Genomics Consortium, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, SE-17177 Stockholm, Sweden.
Jemth AS
No affiliation info available
Collins R
No affiliation info available
Loseva O
No affiliation info available
Johansson A
No affiliation info available
Markova N
No affiliation info available
Hammarström M
No affiliation info available
Flores A
No affiliation info available
Holmberg-Schiavone L
No affiliation info available
Weigelt J
No affiliation info available
Helleday T
No affiliation info available
Schüler H
No affiliation info available
Karlberg T
No affiliation info available

MeSH

BiocatalysisCrystallography, X-RayEnzyme InhibitorsHumansModels, MolecularPoly(ADP-ribose) Polymerase InhibitorsPoly(ADP-ribose) PolymerasesProtein ConformationSubstrate Specificity

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19354255

Citation

Lehtiö, Lari, et al. "Structural Basis for Inhibitor Specificity in Human poly(ADP-ribose) Polymerase-3." Journal of Medicinal Chemistry, vol. 52, no. 9, 2009, pp. 3108-11.
Lehtiö L, Jemth AS, Collins R, et al. Structural basis for inhibitor specificity in human poly(ADP-ribose) polymerase-3. J Med Chem. 2009;52(9):3108-11.
Lehtiö, L., Jemth, A. S., Collins, R., Loseva, O., Johansson, A., Markova, N., Hammarström, M., Flores, A., Holmberg-Schiavone, L., Weigelt, J., Helleday, T., Schüler, H., & Karlberg, T. (2009). Structural basis for inhibitor specificity in human poly(ADP-ribose) polymerase-3. Journal of Medicinal Chemistry, 52(9), 3108-11. https://doi.org/10.1021/jm900052j
Lehtiö L, et al. Structural Basis for Inhibitor Specificity in Human poly(ADP-ribose) Polymerase-3. J Med Chem. 2009 May 14;52(9):3108-11. PubMed PMID: 19354255.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Structural basis for inhibitor specificity in human poly(ADP-ribose) polymerase-3. AU - Lehtiö,Lari, AU - Jemth,Ann-Sofie, AU - Collins,Ruairi, AU - Loseva,Olga, AU - Johansson,Andreas, AU - Markova,Natalia, AU - Hammarström,Martin, AU - Flores,Alex, AU - Holmberg-Schiavone,Lovisa, AU - Weigelt,Johan, AU - Helleday,Thomas, AU - Schüler,Herwig, AU - Karlberg,Tobias, PY - 2009/4/10/entrez PY - 2009/4/10/pubmed PY - 2009/6/3/medline SP - 3108 EP - 11 JF - Journal of medicinal chemistry JO - J Med Chem VL - 52 IS - 9 N2 - Poly(ADP-ribose) polymerases (PARPs) activate DNA repair mechanisms upon stress- and cytotoxin-induced DNA damage, and inhibition of PARP activity is a lead in cancer drug therapy. We present a structural and functional analysis of the PARP domain of human PARP-3 in complex with several inhibitors. Of these, KU0058948 is the strongest inhibitor of PARP-3 activity. The presented crystal structures highlight key features for potent inhibitor binding and suggest routes for creating isoenzyme-specific PARP inhibitors. SN - 1520-4804 UR - https://www.unboundmedicine.com/medline/citation/19354255/Structural_basis_for_inhibitor_specificity_in_human_poly_ADP_ribose__polymerase_3_ L2 - https://doi.org/10.1021/jm900052j DB - PRIME DP - Unbound Medicine ER -