The structural response of Human Serum Albumin to oxidation: a biological buffer to local formation of hypochlorite

The most abundant plasma protein, human serum albumin (HSA), plays a key part in the body’s antioxidant defense against reactive species [1]. This study was aimed at correlating oxidant-induced chemical and structural effects on HSA [2]. Despite the chemical modification induced by the oxidant hypochlorite, the native shape is preserved up to oxidant/HSA molar ratio <80, above which a structural transition occurs in the critical range 80−120. This conformational variation involves the drifting of one of the end-domains from the rest of the protein and corresponds to the loss of one-third of the α-helix and a net increase of the protein negative charge. The transition is highly reproducible suggesting that it represents a well-defined structural response typical of this multidomain protein. The ability to tolerate high levels of chemical modification in a folded or only partially unfolded state, as well as the stability to aggregation, provides albumin with optimal features as a biological buffer for the local formation of oxidants