3C49

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

3C49 の概要

• エントリーDOI: 10.2210/pdb3c49/pdb
• 関連するPDBエントリー: 2PA9 3C49
• 分子名称: Poly(ADP-ribose) polymerase 3, 4-[3-(1,4-diazepan-1-ylcarbonyl)-4-fluorobenzyl]phthalazin-1(2H)-one (3 entities in total)
• 機能のキーワード: enzyme-inhibitor complex, catalytic fragment, structural genomics, structural genomics consortium, sgc, alternative splicing, glycosyltransferase, nad, nucleus, transferase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Nucleus: Q9Y6F1
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 40132.49

構造登録者

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) (登録日: 2008-01-29, 公開日: 2008-02-12, 最終更新日: 2023-08-30)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.8 Å)