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. http://www.umass.edu/molvis/martz/lectures/labmolgen/ 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). -Eric /* - - - - - - - - - - - - - - - - - - - - - - - - - - - Eric Martz, Professor Emeritus, Dept Microbiology U Mass, Amherst -- http://www.umass.edu/molvis/martz Biochem 3D Education Resources http://MolviZ.org See 3D Molecules, Install Nothing! - http://firstglance.jmol.org Protein Explorer - 3D Visualization: http://proteinexplorer.org Workshops: http://workshops.proteinexplorer.org World Index of Molecular Visualization Resources: http://molvisindex.org ConSurf - Find Conserved Patches in Proteins: http://consurf.tau.ac.il Atlas of Macromolecules: http://atlas.proteinexplorer.org PDB Lite Macromolecule Finder: http://pdblite.org Molecular Visualization EMail List (molvis-list): http://bioinformatics.org/mailman/listinfo/molvis-list - - - - - - - - - - - - - - - - - - - - - - - - - - - */