4K1H: Induced Opening Of Influenza Virus Neuraminidase N2 150-loop Suggests An Important Role In Inhibitor Binding

Citation:
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.
PDB ID: 4K1HDownload
MMDB ID: 110743
PDB Deposition Date: 2013/4/5
Updated in MMDB: 2013/06
Experimental Method:
x-ray diffraction
Resolution: 1.8  Å
Source Organism:
Similar Structures:
Biological Unit for 4K1H: tetrameric; determined by author and by software (PISA)
Molecular Components in 4K1H
Label Count Molecule
Proteins (4 molecules)
4
Neuraminidase
Molecule annotation
Chemicals (22 molecules)
1
4
2
14
3
2
4
2
* Click molecule labels to explore molecular sequence information.

Citing MMDB
.