4K1I

Induced opening of influenza virus neuraminidase N2 150-loop suggests an important role in inhibitor binding

Summary for 4K1I

• Entry DOI: 10.2210/pdb4k1i/pdb
• Related: 4K1H 4K1J 4K1K
• Descriptor: Neuraminidase, alpha-D-mannopyranose-(1-3)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, CALCIUM ION, ... (6 entities in total)
• Functional Keywords: beta-propeller, glycoside hydrolase enzymes, hydrolase
• Biological source: Influenza A virus
• Total number of polymer chains: 2
• Total formula weight: 88698.18

Authors

Wu, Y.,Gao, F.,Qi, J.X.,Gao, G.F. (deposition date: 2013-04-05, release date: 2013-06-05, Last modification date: 2024-10-16)

Primary citation

Wu, Y.,Qin, G.,Gao, F.,Liu, Y.,Vavricka, C.J.,Qi, J.,Jiang, H.,Yu, K.,Gao, G.F.
Induced opening of influenza virus neuraminidase N2 150-loop suggests an important role in inhibitor binding
Sci Rep, 3:1551-1551, 2013

PubMed Abstract: The recently discovered 150-cavity (formed by loop residues 147-152, N2 numbering) adjacent to the enzymatic active site of group 1 influenza A neuraminidase (NA) has introduced a novel target for the design of next-generation NA inhibitors. However, only group 1 NAs, with the exception of the 2009 pandemic H1N1 NA, possess a 150-cavity, and no 150-cavity has been observed in group 2 NAs. The role of the 150-cavity played in enzymatic activity and inhibitor binding is not well understood. Here, we demonstrate for the first time that oseltamivir carboxylate can induce opening of the rigid closed N2 150-loop and provide a novel mechanism for 150-loop movement using molecular dynamics simulations. Our results provide the structural and biophysical basis of the open form of 150-loop and illustrates that the inherent flexibility and the ligand induced flexibility of the 150-loop should be taken into consideration for future drug design.

PubMed: 23531861
DOI: 10.1038/srep01551

Experimental method

X-RAY DIFFRACTION (1.8 Å)