1WOK

Crystal structure of catalytic domain of human poly(ADP-ribose) polymerase complexed with a quinoxaline-type inhibitor

Summary for 1WOK

• Entry DOI: 10.2210/pdb1wok/pdb
• Related: 1UK0
• Descriptor: Poly [ADP-ribose] polymerase-1, 3-(4-CHLOROPHENYL)QUINOXALINE-5-CARBOXAMIDE (2 entities in total)
• Functional Keywords: protein-inhibitor complex, transferase
• Biological source: Homo sapiens (human)
• Cellular location: Nucleus : P09874
• Total number of polymer chains: 4
• Total formula weight: 157922.30

Authors

Iwashita, A.,Hattori, K.,Yamamoto, H.,Ishida, J.,Kido, Y.,Kamijo, K.,Murano, K.,Miyake, H.,Kinoshita, T.,Warizaya, M.,Ohkubo, M.,Matsuoka, N.,Mutoh, S. (deposition date: 2004-08-20, release date: 2005-03-15, Last modification date: 2023-10-25)

Primary citation

Iwashita, A.,Hattori, K.,Yamamoto, H.,Ishida, J.,Kido, Y.,Kamijo, K.,Murano, K.,Miyake, H.,Kinoshita, T.,Warizaya, M.,Ohkubo, M.,Matsuoka, N.,Mutoh, S.
Discovery of quinazolinone and quinoxaline derivatives as potent and selective poly(ADP-ribose) polymerase-1/2 inhibitors.
Febs Lett., 579:1389-1393, 2005

PubMed Abstract: Two classes of quinazolinone derivatives and quinoxaline derivatives were identified as potent and selective poly(ADP-ribose) polymerase-1 and 2 (PARP-1) and (PARP-2) inhibitors, respectively. In PARP enzyme assays using recombinant PARP-1 and PARP-2, quinazolinone derivatives displayed relatively high selectivity for PARP-1 and quinoxaline derivatives showed superior selectivity for PARP-2. SBDD analysis via a combination of X-ray structural study and homology modeling suggested distinct interactions of inhibitors with PARP-1 and PARP-2. These findings provide a new structural framework for the design of selective inhibitors for PARP-1 and PARP-2.

PubMed: 15733846
DOI: 10.1016/j.febslet.2005.01.036

Experimental method

X-RAY DIFFRACTION (3 Å)