For cya1 even the more conservative mutation identified, already removes some of the catalytic sites in the conserved CyaA domain of the protein, and thus probably inhibit its function.
Indeed, when cut-off thresholds of 0.005 or 0.01 were set, ViVan generated more conservative mutation profiles that more closely resembled previously reported values for wild type and low fidelity variants obtained by molecular clone sequencing(Gnädig et al., 2012; Levi et al., 2010).
The more conservative E710Q mutation showed a phenotype intermediate between WT and E710A and was not studied in detail.
The more conservative G342A mutation did not affect the level of binding to ANTXR2, but ANTXR2-bound PA-G342A prepores exhibited a pH threshold higher than that of wild-type prepores.
As expected, the phenotype (represented by an amino acid series or peptide) is more conservative to changes (mutation) than the genotype.
A second much more conservative de novo mutation in DOCK8 was not predicted to be consequential.
The CDR regions accumulated more non-conservative mutations than any other region, in particular both CDR1 and CDR3 for AL Vκ and Vλ.
At both positions, we studied the alanine replacement and also the more conservative E710Q and Y766F mutations.
The charge-reversing E650R mutation caused a slight left-shift of the dose response curve of cadmium activation, in contrast to the right-shift observed with the more conservative size-preserving E650Q mutation, further supporting the notion that this residue does not directly coordinate metal ions but rather works downstream of metal ion binding for channel activation.
Thus, either all 23 Su var) genes do not influence TPE, or to take a far more conservative interpretation, if these 23 mutations represent only eight distinct loci, each with multiple alleles, then none of the eight Su var) loci suppress TPE.
