Entamoeba histolytica: Structural elucidation of a Major Surface Protease unrelated to the Trypanosomatidae Family Paulo Henrique Matayoshi Calixto

Abstract

Entamoeba histolytica is a protozoan that causes a disease called amebiasis. In most cases, amebiasis behaves as an asymptomatic disease. However, in approximately 10% of cases,
amebiasis presents symptoms, ranging from dysentery and colitis to symptoms resulting from the invasive form of the disease, such as liver dysfunctions. The interaction of this parasite with the human host involves a refined and intimate parasite-host relationship. These types of relationships, almost totally, are governed by surface molecules. One of these molecules is the Major Surface Protease, a zinc-dependent metalloprotease. The objective of this study was to determine and characterize the three-dimensional structure E. histolytca MSP. For the structural determination, the comparative modeling technique was employed. The Leishmania major MSP was used as the template structure, whose identity and similarity
percentages were 28 and 45%, respectively. The E. histotylica MSP presented as a compact structure and divided into three major domains: N-terminal, central and C-terminal. The
structure also presented all the necessary elements for its processing, as well as for the performance of the protease activity. Interestingly, the pattern of surface charge distribution of E. histolytica MSP is the opposite of the pattern observed in L. major MSP, suggesting that both proteases do not share the same substrate.