Structural biology of cysteine biosynthetic pathway enzymes

Abstract

The cysteine biosynthetic pathway is of central importance for the growth, survival, and pathogenicity of the anaerobic protozoan parasite Entamoeba histolytica. This pathway is present across all species but is absent in mammals. Cysteine, the product of this pathway, is the only antioxidative thiol responsible for fighting oxidative stress in E. histolytica. Serine acetyl transferase (SAT) and O -acetyl serine sulfhydrylase (OASS) are the two enzymes catalyzing the de novo cysteine biosynthetic pathway. In all organisms in which so far this pathway is known to exist, both these enzymes associate to form a regulatory complex, but in E. histolytica this complex is not formed. The cysteine biosynthetic pathway has been optimized in this organism to adapt to and fulfill its cysteine requirements. Here we describe recent studies of the structure, function, and complex formation of cysteine biosynthetic enzymes in E. histolytica. The findings reveal subtle modifications that lend both cysteine biosynthetic enzymes their unique characteristics to escape inhibitory regulation; allowing E. histolytica to maintain high levels of cysteine at all times.