Structure of the cystathionine γ-synthase MetB from Mycobacterium ulcerans

摘要

Cystathionine γ-synthase (CGS) is a transulfurication enzyme that catalyzes the first specific step in l-methionine biosynthesis by the reaction of O ⁴-succinyl-l-­homoserine and l-cysteine to produce l-cystathionine and succinate. Controlling the first step in l-methionine biosythesis, CGS is an excellent potential drug target. Mycobacterium ulcerans is a slow-growing mycobacterium that is the third most common form of mycobacterial infection, mainly infecting people in Africa, Australia and Southeast Asia. Infected patients display a variety of skin ailments ranging from indolent non-ulcerated lesions as well as ulcerated lesions. Here, the crystal structure of CGS from M. ulcerans covalently linked to the cofactor pyridoxal phosphate (PLP) is reported at 1.9 Å resolution. A second structure contains PLP as well as a highly ordered HEPES molecule in the active site acting as a pseudo-ligand. These results present the first structure of a CGS from a mycobacterium and allow comparison with other CGS enzymes. This is also the first structure reported from the pathogen M. ulcerans.