8eo2

Structural highlights

Function

LUFX_LUTLO Sand fly salivary protein with antithrombotic, and anti-complement (alternative pathway) activities (PubMed:22796577, PubMed:28912782). Is a slow, tight, non-competitive, and reversible inhibitor of factor Xa (FXa, F10) (PubMed:22796577). Is specific for FXa (Kd=3.86 nM) and does not interact with non-activated FX, or all other enzymes tested (PubMed:22796577). In addition, it blocks prothrombinase and increases both prothrombin time and activated partial thromboplastin time (PubMed:22796577). It also prevents protease-activated receptor 2 (F2RL1, PAR2) activation by FXa (PubMed:22796577). In vivo, it abrogates edema formation triggered by injection of FXa in the paw of mice (PubMed:22796577). Moreover, it prevents FeCl3-induced carotid artery thrombus formation and prolongs activated partial thromboplastin time ex vivo, implying that it works as an anticoagulant in vivo (PubMed:22796577). It also inhibits the early steps of the alternative pathway of complement by direct binding to the proconvertase C3b-B complex, by inhibiting activation of factor B and consequently the formation of the C3 convertase (PubMed:28912782).^{[1] [2]}

References

1. ↑ Collin N, Assumpção TC, Mizurini DM, Gilmore DC, Dutra-Oliveira A, Kotsyfakis M, Sá-Nunes A, Teixeira C, Ribeiro JM, Monteiro RQ, Valenzuela JG, Francischetti IM. Lufaxin, a novel factor Xa inhibitor from the salivary gland of the sand fly Lutzomyia longipalpis blocks protease-activated receptor 2 activation and inhibits inflammation and thrombosis in vivo. Arterioscler Thromb Vasc Biol. 2012 Sep;32(9):2185-98. PMID:22796577 doi:10.1161/ATVBAHA.112.253906
2. ↑ Mendes-Sousa AF, do Vale VF, Silva NCS, Guimaraes-Costa AB, Pereira MH, Sant'Anna MRV, Oliveira F, Kamhawi S, Ribeiro JMC, Andersen JF, Valenzuela JG, Araujo RN. The Sand Fly Salivary Protein Lufaxin Inhibits the Early Steps of the Alternative Pathway of Complement by Direct Binding to the Proconvertase C3b-B. Front Immunol. 2017 Aug 31;8:1065. PMID:28912782 doi:10.3389/fimmu.2017.01065