2c97: Difference between revisions
No edit summary |
No edit summary |
||
| Line 5: | Line 5: | ||
==Overview== | ==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 ... | 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== | ||
2C97 is a | 2C97 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis] with K, ACT, JCL, DTD and MPD as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Riboflavin_synthase Riboflavin synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.5.1.9 2.5.1.9] Structure known Active Site: AC1. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2C97 OCA]. | ||
==Reference== | ==Reference== | ||
| Line 34: | Line 34: | ||
[[Category: transferase]] | [[Category: transferase]] | ||
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 5 14:26:25 2007'' | ||