Analysis of pKa shifts
It is well established that pKa values of residues can shift their
values due to different structural and environmental features43.
Residues with pKa shifts could be involved in critical roles in
catalytic mechanisms, protein-protein interactions, and ligand binding
and could be associated with the support of several biological functions44.
We analyzed the occurrence of pKa shifts as a proxy to detect residues
involved in the biological process. From the analysis of the pKa values
of the ionizable residues in all the available albumins conformers
with known structure, we were able to detect the presence of activated
amino acids in the cavity where the putative active site occurs in HSA.
In particular, residues Lys 199 and Arg 222 described before, showed an
abnormal acid pKa (see Table 1).