Download MendeleyConformational Changes Upon Ligand Binding in the Essential Class II Fumarase Rv1098C from Mycobacterium Tuberculosis.
Mechaly, A.E., Haouz, A., Miras, I., Barilone, N., Weber, P., Shepard, W., Alzari, P.M., Bellinzoni, M.(2012) FEBS Lett 586: 1606
- PubMed: 22561013
- DOI: https://doi.org/10.1016/j.febslet.2012.04.034
- Primary Citation of Related Structures:
4ADL, 4ADM, 4APA, 4APB - PubMed 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.
Organizational Affiliation:
Institut Pasteur, Unité de Microbiologie Structurale and CNRS-UMR3528, 25 rue du Dr. Roux, 75724 Paris cedex 15, France.
