tetano
Editor, Senior Moderator
Acta Crystallogr D Biol Crystallogr. 2014 May;70(Pt 5):1357-65. doi: 10.1107/S1399004714002971. Epub 2014 Apr 30.
Structural basis of sialidase in complex with geranylated flavonoids as potent natural inhibitors.
Lee Y1, Ryu YB2, Youn HS1, Cho JK3, Kim YM2, Park JY2, Lee WS2, Park KH3, Eom SH1.
Author information
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.
KEYWORDS:
NanI, diplacone, geranylated flavonoid, sialidase, sialidase inhibitor
PMID:
24816104
[PubMed - in process]
http://www.ncbi.nlm.nih.gov/pubmed/24816104
Structural basis of sialidase in complex with geranylated flavonoids as potent natural inhibitors.
Lee Y1, Ryu YB2, Youn HS1, Cho JK3, Kim YM2, Park JY2, Lee WS2, Park KH3, Eom SH1.
Author information
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.
KEYWORDS:
NanI, diplacone, geranylated flavonoid, sialidase, sialidase inhibitor
PMID:
24816104
[PubMed - in process]
http://www.ncbi.nlm.nih.gov/pubmed/24816104