He swept into power on an anti-establishment wave of conservative change, and is working to cast himself as an outside-the-Beltway crusader even though he has served in Congress for two decades.
However, given that the mutation represents a relatively conservative change, and is far from the protease domain, at least some of the phenotypes seen in rsw4 might reflect gain-of-function effects due to the presence of an aberrant protein.
The P125A-mutation is not a conservative change and would be expected to alter peptide folding around the mutation site.
However, the change from aspartic acid in the human S100A7 to a glutamic acid in mouse S100A7/psoriasin is a conservative change and the residue remains acidic.
Our mutagenic analysis employed a series of conservative or non-conservative changes, and so was used to assess the binding phenotypes induced by residues present in other FIV isolates (Figure 5A).
However, the remaining 6 have non-conservative changes, and two of these (FTT0905, a Type IV pili glycosylation protein, and FTT1156c, pilQ) have 5 and 6 non-conservative amino-acid changes, respectively.
We chose to use the most stringent CPDL criteria and therefore individually engineered into the parent enzyme the six most dramatic changes, including five non-conservative changes and one position with a difference in amino acid charge between FatAs and FatBs.
The predicted amino acid substitution Val68Gly is a non-conservative change, and Val68 is highly conserved across species (Fig. 5C).
Two of these are conservative changes (Val87Ile and Leu361Ile) while two others entail substitution of an alanine for another small residue (Ala326Cys and Ala342Ser); the remaining pair of substitutions (Pro161Ala, Ala189Pro), while not so obviously conservative, can readily be accommodated within the protein core as judged from their excellent packing scores.
