Rama Ranganathan, some initial synthesis of NSF proposal and more

Dr. Ramaganathan gave a very fascinating seminar today:

first some of his work:

Spatial Localization of the K Channel Selectivity Filter by Mutant Cycle–Based Structure AnalysisFind It @ MUgroup of 4 »
R Ranganathan, JH Lewis, R MacKinnon – Cell, 2002 – neuron.org
The structurally well-characterized scorpion toxin Agitoxin2 inhibits ion
permeation through Shaker K + channels by binding to the external pore
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Evolutionarily conserved pathways of energetic connectivity in protein families.Find It @ MUgroup of 2 »
SW Lockless, R Ranganathan – Science, 1999 – ncbi.nlm.nih.gov
For mapping energetic interactions in proteins, a technique was developed that
uses evolutionary data for a protein family to measure statistical
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Structural and functional analysis of the mitotic rotamase Pin1 suggests substrate recognition is …Find It @ MUgroup of 7 »
R Ranganathan, KP Lu, T Hunter, JP Noel – Cell, 1997 – research.caregroup.org
Rama Ranganathan,* § Kun Ping Lu, †‡ et al., 1994). Cyclin B is expressed
starting at the end of the S phase and must be degraded in a ubiquitin-
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The structural basis for red fluorescence in the tetrameric GFP homolog DsRedFind It @ MUgroup of 4 »
MA Wall, M Socolich, R Ranganathan – Nature Structural Biology, 2000 – nature.com
Aquatic species such as jellyfish, sea anemones, and coral display an extensive
palette of visible fluorescence and coloring. In part, the vibrant
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Arrestin function in inactivation of G protein-coupled receptor rhodopsin in vivoFind It @ MUgroup of 4 »
PJ Dolph, R Ranganathan, NJ Colley, RW Hardy, M … – Science, 1993 – sciencemag.org
Arrestins have been implicated in the regulation of many G protein-coupled
receptor signaling cascades. Mutations in two Drosophila
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Second some implications:

phylogenetic analysis can reveal groups of conserved residues that seem to imply coevolution and hence their essentiality in function(one thing to note that he stated that at least 80-100 residues are necessary for appropriate results.   Using this analysis can reveal residues that may not be directly linked to the active site of an enzyme but may be involved in changing kinetics via allosteric regulation. He used this method to look at WW domains and PDZ proteins(find references) which demonstrated its pragmatic use.

After thoughts/questions?

How conserved are the NRF2 and KEAP1 proteins throughtout organisms?

NRF3 is an inhibitor of NRF2 and studies seem to indicate that it simply competes for NRF2 binding.

How could one tease out the mechanism of NRF2 binding?

how similar are NRF2/NRF3 —–> perform blast and multiple alignment.

 Anouther tangent but related(to NSF proposal) thought…

what about alpha lipoic acid?  some studies have found decreased binding of NRF2 as a function of age, while application of ALA can restore this binding. What are some possible mechanims?





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