Intriguingly, G537 is the most commonly mutated residue in HIF-2α driven disease while the substitution of the non-polar, sulfur-containing Met residue with a polar Thr residue supports the notion that HIF-2α peptide might not bind pVHL with an identical motif as HIF-1α.
Both sequence analysis and mutagenesis data suggest that at this position a polar (e.g., T or N) or negatively charged residue supports p53 degradation activity, whereas a positively charged residue (R or K) is generally unfavorable to p53 degradation activity.
A conserved, positively charged residue supports the initial formation of a flavin-semiquinone-superoxide radical pair in some flavin oxidases.
Ileb415 is the hydrophobic residue supporting the V shape of the cofactor that is found in all ThDP-dependent enzymes.
As in loop β2- β3, few glycine residues are also present before a negatively charged residue supporting the hypothesis that correct orientation of charged residues in the specificity loops could be important in receptor recognition.
If only one key residue supported by one of two secondary residues was capable of allowing an SH2 domain to bind, then the chances of randomly generating an SH2 binding site centered around a given tyrosine residue are less than one in a hundred.
In silico analysis of yeast, Toxoplasma, human and mouse proteomes revealed a list of potentially modifiable proteins by virtue of the presence of a predicted N-terminal glycine after potential enzymatic removal of a signal peptide or the initiator methionine residue (Supporting Information Table 1).
Structural and functional similarities, genomic context in operons containing other homologous genes, and distributions of conserved surface residues support the hypothesis that IscU protein domains are homologous (i.e. derived from a common ancestor) with the SufE/YgdK family of [Fe S] cluster assembly proteins.
The sw1 sensitivity in paleognaths has been somewhat controversial, because while microspectrophotometry analysis of the sw1 in ostrich suggests VS [ 18], the 86 F and 90C residues support UVS [ 41].
Where both studies are once again in agreement is on the function of the basic residues in the trigger loop: in neither set of experiments do the effects of mutations to these residues support earlier proposals [ 5, 8] that these function as a general acid.
