2vi5
From Proteopedia
LUMAZINE SYNTHASE FROM MYCOBACTERIUM TUBERCULOSIS BOUND TO N-6-(RIBITYLAMINO)PYRIMIDINE-2,4(1H,3H)-DIONE-5-YL-PROPIONAMIDE
Overview
The penultimate step in the biosynthesis of riboflavin is catalyzed by lumazine synthase. Three metabolically stable analogues of the hypothetical intermediate proposed to arise after phosphate elimination in the lumazine synthase-catalyzed reaction were synthesized and evaluated as lumazine synthase inhibitors. All three intermediate analogues were inhibitors of Mycobacterium tuberculosis lumazine synthase, Bacillus subtilis lumazine synthase, and Schizosaccharomyces pombe lumazine synthase, while one of them proved to be an extremely potent inhibitor of Escherichia coli riboflavin synthase with a Ki of 1.3 nM. The crystal structure of M. tuberculosis lumazine synthase in complex with one of the inhibitors provides a model of the conformation of the intermediate occurring immediately after phosphate elimination, supporting a mechanism in which phosphate elimination occurs before a conformational change of the Schiff base intermediate toward a cyclic structure.
About this Structure
2VI5 is a Single protein structure of sequence from Mycobacterium tuberculosis. Full crystallographic information is available from OCA.
Reference
A New Series of N-[2,4-Dioxo-6-d-ribitylamino-1,2,3,4-tetrahydropyrimidin-5-yl]oxalamic Acid Derivatives as Inhibitors of Lumazine Synthase and Riboflavin Synthase: Design, Synthesis, Biochemical Evaluation, Crystallography, and Mechanistic Implications., Zhang Y, Illarionov B, Morgunova E, Jin G, Bacher A, Fischer M, Ladenstein R, Cushman M, J Org Chem. 2008 Apr 4;73(7):2715-2724. Epub 2008 Mar 11. PMID:18331058
