2c97: Difference between revisions
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==Overview== | ==Overview== | ||
Recently published genomic investigations of the human pathogen | 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. | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: transferase]] | [[Category: transferase]] | ||
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Revision as of 17:46, 21 February 2008
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LUMAZINE SYNTHASE FROM MYCOBACTERIUM TUBERCULOSIS BOUND TO 4-(6-CHLORO-2,4-DIOXO-1,2,3,4-TETRAHYDROPYRIMIDIN-5-YL) BUTYL PHOSPHATE
OverviewOverview
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.
About this StructureAbout this Structure
2C97 is a Single protein structure of sequence from Mycobacterium tuberculosis with , , , and as ligands. Active as Riboflavin synthase, with EC number 2.5.1.9 Known structural/functional Site: . Full crystallographic information is available from OCA.
ReferenceReference
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
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