title: Structure of the cystathionine γ-synthase MetB from Mycobacterium ulcerans.
abstract: 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.
authors: Seattle Structural Genomics Center for Infectious Disease (SSGCID), USA. mclifton@embios.com
authors: Matthew C
authors: MC
authors: Clifton
authors: Jan
authors: J
authors: Abendroth
authors: Thomas E
authors: TE
authors: Edwards
authors: David J
authors: DJ
authors: Leibly
authors: Angela K
authors: AK
authors: Gillespie
authors: Micah
authors: M
authors: Ferrell
authors: Shellie H
authors: SH
authors: Dieterich
authors: Ilyssa
authors: I
authors: Exley
authors: Bart L
authors: BL
authors: Staker
authors: Peter J
authors: PJ
authors: Myler
authors: Wesley C
authors: WC
authors: Van Voorhis
authors: Lance J
authors: LJ
authors: Stewart
mesh_terms: D019757:Carbon-Oxygen Lyases / Q000737:chemistry*; D020134:Catalytic Domain; D008958:Models, Molecular; D019911:Mycobacterium ulcerans / Q000201:enzymology*; D020836:Protein Structure, Quaternary; D055672:Static Electricity
chemical_list: C022696:O-succinylhomoserine (thiol)-lyase; D019757:Carbon-Oxygen Lyases