Biochemistry 6. The mythical protein furiosan (a protein that’s expression is hi
ID: 52980 • Letter: B
Question
Biochemistry
6. The mythical protein furiosan (a protein that’s expression is highly upregulated in drought-like conditions) contains primarily a-helical structure under normal conditions, but upon cleavage of the 20 residues at the C-terminus by the enzyme immortanase, the protein refolds to contain predominantly b-sheet structure. The aggregation of this protein results in a variety of symptoms: pale skin, hair loss, anemia (constant need for blood transfusions), increased reckless decision making, and the patients’ insatiable (and inexplicable) desire to spray silver paint on their mouths when under duress. (a) You are a chemical biologist—design a drug/method to inhibit the aggregation of this protein. (b) How would you determine whether or not the protein was aggregated?
Explanation / Answer
A) The method/drug to inhibit the aggregation of furiosan can be done either by competitive inhibiton of the enzyme immortanse. Or by analysis the amino acid sequence of immortanase by Edman degradation and then afterwards the sequence of the gene is determined. RNA silencing methods can then be designed to silence the mRNA of this gene. THis can be done by using a Recombinant vector containing the complementary RNA sequence.
B) The aggregation of the protein can simply be detrmined by obtaining and purifying a sample of this protein from the patient and running it on an SDS-PAGE. The size of the aggregated protein will be 20 residues smaller than the non-aggregated protein.
NMR spectroscopy and X-ray Crystallization can also be used.
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