Abstract:The biological function of lipoprotein(a) [Lp(a)] remains elusive although it was identified in 1963. We previously hypothesized that Lp(a) might inhibit pathogens from hijacking host plasminogen (Plg) since apolipoprotein(a) [Apo(a)], a unique protein in Lp(a), shares a high homology with Plg. We demonstrate that Lp(a) bound to recombinant Streptococcal α-enolase (rSEN), which is a surface Plg receptor on group A Streptococcus (GAS). However, recombinant C-terminal lysines-deleted variant of enolase (rSEN∆434-435) did not bind to Lp(a). Moreover, epsilon-aminocaproic acid (EACA), a lysine analog, significantly inhibited the binding of rSEN to Lp(a). Collectively, Lp(a) via its LBS bound to the C-terminal lysines of rSEN. In addition, Lp(a) only competitively blocked the Plg-rSEN interaction but not Plg-rSEN∆434-435 interaction since Plg could also bind to the internal lysine residue of α-enolase. The preliminary study indicated that Lp(a) also interacted with GAS, consequently competitively inhibiting the Plg-GAS binding to some extent. Therefore, Lp(a) might play a limited role in preventing GAS infection since it only partially inhibited the pathogen from recruiting host Plg.