Bulletin of the Korean Chemical Society

Korean Chemical Society (대한화학회)
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Docking Study of Flavonols and Human c-Jun N-terminal Kinase 1

  • Lee, Jee-Young (Department of Bioscience and Biotechnology, Bio/Molecular Informatics Center, Konkuk University) ;
  • Jeong, Ki-Woong (Department of Bioscience and Biotechnology, Bio/Molecular Informatics Center, Konkuk University) ;
  • Heo, Yong-Seok (Department of Chemistry, Konkuk University) ;
  • Kim, Yang-Mee (Department of Bioscience and Biotechnology, Bio/Molecular Informatics Center, Konkuk University)
  • Received : 2010.06.21
  • Accepted : 2010.06.24
  • Published : 2010.08.20
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Abstract

c-Jun N-terminal kinase 1 (JNK1) is involved in apoptosis, cell differentiation and proliferation. It has been reported that a flavonol, quercetin, induces cell apoptosis and JNK inhibition. In order to understand the interactions of quercetin and JNK1, we performed receptor-oriented pharmacophore based in silico screening and determined a binding model of human JNK1 and quercetin at the ATP binding site of JNK1. 5-OH of A-ring and carbonyl oxygen of C-ring of quercetin participated in hydrogen bonding interactions with backbone of E109 and M111. Additionally, 3'-OH of quercetin formed a hydrogen bond with backbone of I32. One hydrophobic interaction is related on the binding of quercetin to JNK1 with I32, N114, and V158. Based on this model, we conducted a docking study with other 8 flavonols to find possible flavonoids inhibitors of JNK1. We proposed that one flavonols, rhamnetin, can be a potent inhibitor of JNK and 5-OH of A-ring and 3'-OH of B-ring of flavonols are the essential features for JNK1 inhibition.

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References

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