title: Conformational changes upon ligand binding in the essential class II fumarase Rv1098c from Mycobacterium tuberculosis.
abstract: rv1098c, an essential gene in Mycobacterium tuberculosis, codes for a class II fumarase. We describe here the crystal structure of Rv1098c in complex with l-malate, fumarate or the competitive inhibitor meso-tartrate. The models reveal that substrate binding promotes the closure of the active site through conformational changes involving the catalytic SS-loop and the C-terminal domain, which likely represents a general feature of this enzyme superfamily. Analysis of ligand-enzyme interactions as well as site-directed mutagenesis suggest Ser318 as one of the two acid-base catalysts.
authors.affiliation: Institut Pasteur, Unité de Microbiologie Structurale and CNRS-UMR3528, 25 rue du Dr. Roux, 75724 Paris cedex 15, France.
authors.forename: Ariel E
authors.initials: AE
authors.lastname: Mechaly
authors.forename: Ahmed
authors.initials: A
authors.lastname: Haouz
authors.forename: Isabelle
authors.initials: I
authors.lastname: Miras
authors.forename: Nathalie
authors.initials: N
authors.lastname: Barilone
authors.forename: Patrick
authors.initials: P
authors.lastname: Weber
authors.forename: William
authors.initials: W
authors.lastname: Shepard
authors.forename: Pedro M
authors.initials: PM
authors.lastname: Alzari
authors.forename: Marco
authors.initials: M
authors.lastname: Bellinzoni
mesh_terms: D055162:Biocatalysis; D020134:Catalytic Domain; D005649:Fumarate Hydratase / Q000737:chemistry* / Q000378:metabolism*; D005650:Fumarates / Q000378:metabolism; D008024:Ligands; D008293:Malates / Q000378:metabolism; D008958:Models, Molecular; D009169:Mycobacterium tuberculosis / Q000201:enzymology*; D011485:Protein Binding; D013644:Tartrates / Q000378:metabolism
chemical_list: D005650:Fumarates; D008024:Ligands; D008293:Malates; D013644:Tartrates; C030298:malic acid; D005649:Fumarate Hydratase; C029768:tartaric acid