3C49

Human poly(ADP-ribose) polymerase 3, catalytic fragment in complex with an inhibitor KU0058948

Summary for 3C49

• Entry DOI: 10.2210/pdb3c49/pdb
• Related: 2PA9 3C49
• Descriptor: Poly(ADP-ribose) polymerase 3, 4-[3-(1,4-diazepan-1-ylcarbonyl)-4-fluorobenzyl]phthalazin-1(2H)-one (3 entities in total)
• Functional Keywords: enzyme-inhibitor complex, catalytic fragment, structural genomics, structural genomics consortium, sgc, alternative splicing, glycosyltransferase, nad, nucleus, transferase
• Biological source: Homo sapiens (human)
• Cellular location: Nucleus: Q9Y6F1
• Total number of polymer chains: 1
• Total formula weight: 40132.49

Authors

Lehtio, L.,Karlberg, T.,Arrowsmith, C.H.,Berglund, H.,Bountra, C.,Busam, R.,Collins, R.,Dahlgren, L.G.,Edwards, A.M.,Flodin, S.,Flores, A.,Graslund, S.,Hammarstrom, M.,Helleday, T.,Herman, M.D.,Johansson, A.,Johansson, I.,Kallas, A.,Kotenyova, T.,Moche, M.,Nilsson, M.E.,Nordlund, P.,Nyman, T.,Persson, C.,Sagemark, J.,Svensson, L.,Thorsell, A.G.,Tresaugues, L.,Van den Berg, S.,Welin, M.,Weigelt, J.,Structural Genomics Consortium (SGC) (deposition date: 2008-01-29, release date: 2008-02-12, Last modification date: 2023-08-30)

Primary citation

Lehtio, L.,Jemth, A.S.,Collins, R.,Loseva, O.,Johansson, A.,Markova, N.,Hammarstrom, M.,Flores, A.,Holmberg-Schiavone, L.,Weigelt, J.,Helleday, T.,Schuler, H.,Karlberg, T.
Structural basis for inhibitor specificity in human poly(ADP-ribose) polymerase-3.
J.Med.Chem., 52:3108-3111, 2009

PubMed 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.

PubMed: 19354255
DOI: 10.1021/jm900052j

Experimental method

X-RAY DIFFRACTION (2.8 Å)