[Molvis-list] Avian flu N1 protein structure lesson plan

Eric Martz emartz at microbio.umass.edu
Mon Sep 25 13:52:23 EDT 2006

Dear Colleagues,

Recently, while preparing to teach protein molecular structure and 
structural bioinformatics in two computer lab class meetings for a local 
Lab in Molecular Genetics course, I found a nice current example I thought 
I'd share. Perhaps some of you will want to use this example.

In the Sept 7 Nature, Russell ... Skehel et al. describe the first 3D 
structure for avian flu N1, with and without Tamiflu bound. Tamiflu and 
Relenza were designed in part based on crystallographic structures for 
human flu neuraminidase, so it is fortuitous that they work on avian flu. 
This paper shows that to be somewhat surprising.

The avian flu N1, by itself, has one loop in a different position than the 
human flu structure. Based on this, one might have predicted that the drugs 
would not work on avian N1. However, they do, and the crystal structure of 
the complex shows that Tamiflu induces the protein to fit the drug. The 
errant loop reconfigures itself to nestle up against the drug, completing a 
high-affinity binding pocket.

Also they find a deeper pocket in avian N1 than for human flu. This offers 
a possible target for a new, avian N1-specific drug.

My lesson plan is at the URL below, with links to the paper, PDB codes, 
visualization software (using Jmol, works on all popular browsers and 
computers without installing anything), and Jmol morphs between the 
drug-free and drug-bound structures, animating the induced fit.


The ConSurf server colors a 3D protein molecule with the evolutionary 
conservation level of each amino acid, automatically. It now displays its 
results in Jmol. It shows nice conservation of the catalytic/drug site in 
N1 (links at #5 in the above URL).


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Eric Martz, Professor Emeritus, Dept Microbiology
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