2VI5

LUMAZINE SYNTHASE FROM MYCOBACTERIUM TUBERCULOSIS BOUND TO N-6-(ribitylamino)pyrimidine-2,4(1H,3H)-dione-5-yl-propionamide

Summary for 2VI5

• Entry DOI: 10.2210/pdb2vi5/pdb
• Related: 1W19 1W29 2C92 2C94 2C97 2C9B 2C9D
• Descriptor: 6,7-DIMETHYL-8-RIBITYLLUMAZINE SYNTHASE, 1-deoxy-1-{[(5S)-2,6-dioxo-5-(propanoylamino)-1,2,5,6-tetrahydropyrimidin-4-yl]amino}-D-ribitol, POTASSIUM ION, ... (5 entities in total)
• Functional Keywords: transferase, lumazine synthase, riboflavin biosynthesis, mycobacterium tuberculosis
• Biological source: MYCOBACTERIUM TUBERCULOSIS
• Total number of polymer chains: 10
• Total formula weight: 168734.87

Authors

Morgunova, E.,Zhang, Y.,Jin, G.,Illarionov, B.,Bacher, A.,Fischer, M.,Cushman, M.,Ladenstein, R. (deposition date: 2007-11-27, release date: 2008-04-08, Last modification date: 2023-12-13)

Primary citation

Zhang, Y.,Illarionov, B.,Morgunova, E.,Bacher, A.,Fischer, M.,Ladenstein, R.,Cushman, M.
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 Syntase and Riboflavin Synthase: Design, Synthesis, Biochemical Evaluation, Crystallography and Mechanistic Implications.
J.Org.Chem., 73:2715-, 2008

PubMed Abstract: 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.

PubMed: 18331058
DOI: 10.1021/JO702631A

Experimental method

X-RAY DIFFRACTION (2.3 Å)