Structural and evolutionary analysis unveil functional adaptations in the promiscuous behavior of serum albumins

Promiscuous activities have been related to the capacity to catalyze reactions different from those a protein has evolved to sustain. From this evolutionary perspective, we rethought the serum albumins promiscuous behavior. We found that the cross aldol condensation of acetone and p-formylbenzonitrile is a promiscuous reaction conserved in humans and other mammals. Structural and evolutionary analysis indicates that the involved residues could have evolved for a still unknown biological function. Our results could contribute to better characterize the serum albumin family and raise questions about the evolution of protein promiscuity and function.