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

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Title
Structural basis of sialidase in complex with geranylated flavonoids as potent natural inhibitors
Author(s)
Y Lee; Young Bae Ryu; H S Youn; J K Cho; Young-Min Kim; Ji Young ParkWoo Song Lee; K H Park; S H Eom
Bibliographic Citation
Acta Crystallographica Section D-Biological Crystallography, vol. 70, no. 5, pp. 1357-1365
Publication Year
2014
Abstract
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.
Keyword
diplaconegeranylated flavonoidNanIsialidasesialidase inhibitor
ISSN
0907-4449
Publisher
Int Union Crystallography
DOI
http://dx.doi.org/10.1107/S1399004714002971
Type
Article
Appears in Collections:
Jeonbuk Branch Institute > Functional Biomaterial Research Center > 1. Journal Articles
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