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|Title:||Plasticity of the 340-loop in influenza neuraminidase offers new insight for antiviral drug development||Authors:||Han, Nanyu
Ng, Justin Tze Yang
|Keywords:||Science::Biological sciences||Issue Date:||2020||Source:||Han, N., Ng, J. T. Y., Li, Y., Mu, Y., & Huang, Z. (2020). Plasticity of the 340-Loop in Influenza Neuraminidase Offers New Insight for Antiviral Drug Development. International Journal of Molecular Sciences, 21(16), 5655-. doi:10.3390/ijms21165655||Journal:||International journal of molecular sciences||Abstract:||The recently discovered 340-cavity in influenza neuraminidase (NA) N6 and N7 subtypes has introduced new possibilities for rational structure-based drug design. However, the plasticity of the 340-loop (residues 342-347) and the role of the 340-loop in NA activity and substrate binding have not been deeply exploited. Here, we investigate the mechanism of 340-cavity formation and demonstrate for the first time that seven of nine NA subtypes are able to adopt an open 340-cavity over 1.8 μs total molecular dynamics simulation time. The finding that the 340-loop plays a role in the sialic acid binding pathway suggests that the 340-cavity can function as a druggable pocket. Comparing the open and closed conformations of the 340-loop, the side chain orientation of residue 344 was found to govern the formation of the 340-cavity. Additionally, the conserved calcium ion was found to substantially influence the stability of the 340-loop. Our study provides dynamical evidence supporting the 340-cavity as a druggable hotspot at the atomic level and offers new structural insight in designing antiviral drugs.||URI:||https://hdl.handle.net/10356/146355||ISSN:||1661-6596||DOI:||10.3390/ijms21165655||Rights:||© 2020 The Authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).||Fulltext Permission:||open||Fulltext Availability:||With Fulltext|
|Appears in Collections:||SBS Journal Articles|
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