4HKI

Tankyrase 2 in complex with flavone

Summary for 4HKI

• Entry DOI: 10.2210/pdb4hki/pdb
• Related: 3U9H 3U9Y 3UA9 4HKK 4HKN 4HL5 4HLF 4HLG 4HLH 4HLK 4HLM 4HMH
• Descriptor: Tankyrase-2, ZINC ION, SULFATE ION, ... (8 entities in total)
• Functional Keywords: protein-ligand complex, diphtheria toxin like fold, transferase, adp-ribosylation
• Biological source: Homo sapiens (human); More
• Cellular location: Cytoplasm: Q9H2K2 Q9H2K2
• Total number of polymer chains: 4
• Total formula weight: 55991.50

Authors

Narwal, M.,Haikarainen, T.,Lehtio, L. (deposition date: 2012-10-15, release date: 2012-10-31, Last modification date: 2023-09-20)

Primary citation

Narwal, M.,Haikarainen, T.,Fallarero, A.,Vuorela, P.M.,Lehtio, L.
Screening and structural analysis of flavones inhibiting tankyrases.
J.Med.Chem., 56:3507-3517, 2013

PubMed Abstract: Flavonoids are known for their beneficial effects on human health, and therefore the therapeutic potential of these compounds have been extensively studied. Flavone has been previously identified as a tankyrase inhibitor, and to further elucidate whether tankyrases would be inhibited by other flavonoids, we performed a systematic screening of tankyrase 2 inhibitory activity using 500 natural and naturally derived flavonoids covering nine different flavonoid classes. All identified tankyrase inhibitors were flavones. We report crystal structures of all the hit compounds in complex with the catalytic domain of human tankyrase 2. Flavone derivatives in all 10 crystal structures bind to the nicotinamide binding site of tankyrase 2. Potencies of the active flavones toward tankyrases vary between 50 nM and 1.1 μM, and flavones show up to 200-fold selectivity for tankyrases over ARTD1. The molecular details of the interactions revealed by cocrystal structures efficiently describe the properties of potent flavone derivatives inhibiting tankyrases.

PubMed: 23574272
DOI: 10.1021/jm3018783

Experimental method

X-RAY DIFFRACTION (2.15 Å)