Structural basis of sialidase in complex with geranylated flavonoids as potent natural inhibitors

نویسندگان

  • Youngjin Lee
  • Young Bae Ryu
  • Hyung-Seop Youn
  • Jung Keun Cho
  • Young Min Kim
  • Ji-Young Park
  • Woo Song Lee
  • Ki Hun Park
  • Soo Hyun Eom
چکیده

Sialidase catalyzes the removal of a terminal sialic acid from glycoconjugates and plays a pivotal role in nutrition, cellular interactions and pathogenesis mediating various infectious diseases including cholera, influenza and sepsis. An array of antiviral sialidase agents have been developed and are commercially available, such as zanamivir and oseltamivir for treating influenza. However, the development of bacterial sialidase inhibitors has been much less successful. Here, natural polyphenolic geranylated flavonoids which show significant inhibitory effects against Cp-NanI, a sialidase from Clostridium perfringens, are reported. This bacterium causes various gastrointestinal diseases. The crystal structure of the Cp-NanI catalytic domain in complex with the best inhibitor, diplacone, is also presented. This structure explains how diplacone generates a stable enzyme-inhibitor complex. These results provide a structural framework for understanding the interaction between sialidase and natural flavonoids, which are promising scaffolds on which to discover new anti-sialidase agents.

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منابع مشابه

Structural basis of sialidase in complex with geranylated flavonoids as potent natural inhibitors. Corrigendum

A correction is made to the article by Lee et al. [(2014) Acta Cryst. D70, 1357-1365].

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عنوان ژورنال:

دوره 70  شماره 

صفحات  -

تاریخ انتشار 2014