8DWB

Neuraminidase from influenza virus A/Moscow/10/1999(H3N2) in complex with sialic acid

これはPDB形式変換不可エントリーです。

8DWB の概要

• エントリーDOI: 10.2210/pdb8dwb/pdb
• 分子名称: Neuraminidase, alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (8 entities in total)
• 機能のキーワード: neuraminidase, influenza, viral protein, hydrolase
• 由来する生物種: Influenza A virus (A/Moscow/10/1999(H3N2))
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 45310.08

構造登録者

Lei, R.,Hernandez Garcia, A. (登録日: 2022-08-01, 公開日: 2022-12-21, 最終更新日: 2024-11-20)

主引用文献

Lei, R.,Hernandez Garcia, A.,Tan, T.J.C.,Teo, Q.W.,Wang, Y.,Zhang, X.,Luo, S.,Nair, S.K.,Peng, J.,Wu, N.C.
Mutational fitness landscape of human influenza H3N2 neuraminidase.
Cell Rep, 42:111951-111951, 2023

PubMed Abstract: Influenza neuraminidase (NA) has received increasing attention as an effective vaccine target. However, its mutational tolerance is not well characterized. Here, the fitness effects of >6,000 mutations in human H3N2 NA are probed using deep mutational scanning. Our result shows that while its antigenic regions have high mutational tolerance, there are solvent-exposed regions with low mutational tolerance. We also find that protein stability is a major determinant of NA mutational fitness. The deep mutational scanning result correlates well with mutational fitness inferred from natural sequences using a protein language model, substantiating the relevance of our findings to the natural evolution of circulating strains. Additional analysis further suggests that human H3N2 NA is far from running out of mutations despite already evolving for >50 years. Overall, this study advances our understanding of the evolutionary potential of NA and the underlying biophysical constraints, which in turn provide insights into NA-based vaccine design.

PubMed: 36640354
DOI: 10.1016/j.celrep.2022.111951

実験手法

X-RAY DIFFRACTION (1.602 Å)