Acute phase α1-acid glycoprotein as a siderophore-capturing component of the human plasma: A molecular modeling study

Abstract

Siderophores are ferric ion-specific organic compounds that are used by bacteria and fungi to secure their iron supply when infecting target organisms. There are a few proteins in the human body, named siderocalins, which bind these important virulence factors and so starve microorganisms of iron. In this study, we analyzed in silico if serum α₁-acid glycoprotein (AAG), the major acute phase lipocalin component of the human plasma, could functionally belong to this group. The real biological function of AAG is elusive and its concentration substantially increases in response to pathological stimuli, including bacterial infections. We computationally evaluated the potential binding of nine microbial siderophores into the β-barrel cavity of AAG and compared the results with the corresponding experimental data reported for siderophore-neutrophil gelatinase-associated lipocalin complexes. According to the results, petrobactin and Fe-BisHaCam are putative candidates to be recognized by this protein. It is proposed that AAG may function as a siderophore capturing component of the innate immune system being able to neutralize bacterial iron chelators not recognized by other siderocalins.

Keywords: Molecular docking; Molecular dynamics; Neutrophil gelatinase-associated lipocalin; Parameterization of metal complexes; Petrobactin; Siderocalin; Siderophores; α(1)-acid glycoprotein.