2c9d
From Proteopedia
LUMAZINE SYNTHASE FROM MYCOBACTERIUM TUBERCULOSIS BOUND TO 3-(1,3,7-TRIHYDRO-9-D-RIBITYL-2,6,8-PURINETRIONE-7-YL) HEXANE 1-PHOSPHATE
Overview
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
2C9D is a Single protein structure of sequence from Mycobacterium tuberculosis. Full crystallographic information is available from OCA.
Reference
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 Page seeded by OCA on Sat May 3 21:30:07 2008
