2c94

LUMAZINE SYNTHASE FROM MYCOBACTERIUM TUBERCULOSIS BOUND TO 3-(1,3,7- TRIHYDRO-9-D-RIBITYL-2,6,8-PURINETRIONE-7-YL) 1,1 difluoropentane-1- PHOSPHATELUMAZINE SYNTHASE FROM MYCOBACTERIUM TUBERCULOSIS BOUND TO 3-(1,3,7- TRIHYDRO-9-D-RIBITYL-2,6,8-PURINETRIONE-7-YL) 1,1 difluoropentane-1- PHOSPHATE

Structural highlights 2c94 is a 5 chain structure with sequence from Mycobacterium tuberculosis. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.9Å Ligands: , Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function RISB_MYCTU Catalyzes the formation of 6,7-dimethyl-8-ribityllumazine by condensation of 5-amino-6-(D-ribitylamino)uracil with 3,4-dihydroxy-2-butanone 4-phosphate. This is the penultimate step in the biosynthesis of riboflavin. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed Recently published genomic investigations of the human pathogen Mycobacterium tuberculosis have revealed that genes coding the proteins involved in riboflavin biosynthesis are essential for the growth of the organism. Because the enzymes involved in cofactor biosynthesis pathways are not present in humans, they appear to be promising candidates for the development of therapeutic drugs. The substituted purinetrione compounds have demonstrated high affinity and specificity to lumazine synthase, which catalyzes the penultimate step of riboflavin biosynthesis in bacteria and plants. The structure of M. tuberculosis lumazine synthase in complex with five different inhibitor compounds is presented, together with studies of the binding reactions by isothermal titration calorimetry. The inhibitors showed the association constants in the micromolar range. The analysis of the structures demonstrated the specific features of the binding of different inhibitors. The comparison of the structures and binding modes of five different inhibitors allows us to propose the ribitylpurinetrione compounds with C4-C5 alkylphosphate chains as most promising leads for further development of therapeutic drugs against M. tuberculosis. Structural and thermodynamic insights into the binding mode of five novel inhibitors of lumazine synthase from Mycobacterium tuberculosis.,Morgunova E, Illarionov B, Sambaiah T, Haase I, Bacher A, Cushman M, Fischer M, Ladenstein R FEBS J. 2006 Oct;273(20):4790-804. Epub 2006 Sep 19. PMID:16984393 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

spinqualitylabelsall models 2c94, resolution 1.90Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image