N1 Neuraminidase
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I. Introduction
Neuraminidase is a surface glycoprotein enzyme of
the influenza virus that facilitates virus release and spread of
infection to new cells by removing sialic acid from the virus and other
cellular glycoproteins. There are two classes of neuraminidases.
N1 belongs to group one which is found in the H5N1 avian influenza virus
and threatens a potential pandemic. Neuraminidase exists as a homotetramer. Drugs such as oseltamivir (Tamiflu)
target the neuraminidase enzyme of the virus and mimic the transition
state of the reaction. Each monomer of the tetramer contains an active site which binds the drug.
For more information see
Biochemistry Online: Chapter
3B - Complex Carbohydrates/Glycans and Glycoconjugate
II. General Structure
Homotetramer Displays
Wireframe
Backbone
Backbone and Sidechains
Beta Sheets and Alpha Helices:
Note the canonical six-bladed beta-propeller structure of each monomer.
Hydrogen Bonding
Bound Oseltamivir
Monomer Displays
Active Site Residues:
Influenza neuraminidase active sites conserve the displayed residues.
These residues are important in substrate binding.
Arg 118, Arg 292, and Arg 371 bind the carboxylate of the sialic acid substrate.
Arg 152 interacts with the acetamido group of the substrate.
Glu 276 forms hydrogen bonds with hydroxyl groups of the substrate.
Active Site Residues with Bound Drug
150 Loop: Group one neuraminidases can bind oseltamivir in either an open or closed conformation of the 150 loop
cavity (residues 147-152 shown as thicker wireframe). This cavity is adjacent to the
active site. The neuraminidase initially binds the drug in the open conformation, which is lower energy.
After drug binding the neuraminidase eventually adopts the closed conformation.
150 Loop with Bound Drug
Active Site: Note the interactions of the positively charged Arg residues 292, 371, and 118 with a
carboxyl group of oseltamivir. Also notice the interactions of the 150 loop with
oseltamivir, specifically Arg 152 with a carbonyl and Asp 151 with an amine.