1w29
From Proteopedia
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| - | [[Image:1w29.gif|left|200px]] | + | [[Image:1w29.gif|left|200px]] |
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| - | '''LUMAZINE SYNTHASE FROM MYCOBACTERIUM TUBERCULOSIS BOUND TO 3-(1,3,7-TRIHYDRO-9-D-RIBITYL-2,6,8-PURINETRIONE-7-YL) BUTANE 1-PHOSPHATE''' | + | {{Structure |
| + | |PDB= 1w29 |SIZE=350|CAPTION= <scene name='initialview01'>1w29</scene>, resolution 2.30Å | ||
| + | |SITE= <scene name='pdbsite=AC1:D1d+Binding+Site+For+Chain+E'>AC1</scene> | ||
| + | |LIGAND= <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=TS1:4-{2,6,8-TRIOXO-9-[(2R,3S,4R)-2,3,4,5-TETRAHYDROXYPENTYL]-1,2,3,6,8,9-HEXAHYDRO-7H-PURIN-7-YL}BUTYL+DIHYDROGEN+PHOSPHATE'>TS1</scene>, <scene name='pdbligand=TS0:4-{2,6,8-TRIOXO-9-[(2S,3R,4R)-2,3,4,5-TETRAHYDROXYPENTYL]-1,2,3,6,8,9-HEXAHYDRO-7H-PURIN-7-YL}BUTYL+DIHYDROGEN+PHOSPHATE'>TS0</scene>, <scene name='pdbligand=D1D:(4S,5S)-1,2-DITHIANE-4,5-DIOL'>D1D</scene> and <scene name='pdbligand=ACY:ACETIC ACID'>ACY</scene> | ||
| + | |ACTIVITY= [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] | ||
| + | |GENE= | ||
| + | }} | ||
| + | |||
| + | '''LUMAZINE SYNTHASE FROM MYCOBACTERIUM TUBERCULOSIS BOUND TO 3-(1,3,7-TRIHYDRO-9-D-RIBITYL-2,6,8-PURINETRIONE-7-YL) BUTANE 1-PHOSPHATE''' | ||
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==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1W29 is a [ | + | 1W29 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1W29 OCA]. |
==Reference== | ==Reference== | ||
| - | Crystal structure of lumazine synthase from Mycobacterium tuberculosis as a target for rational drug design: binding mode of a new class of purinetrione inhibitors., Morgunova E, Meining W, Illarionov B, Haase I, Jin G, Bacher A, Cushman M, Fischer M, Ladenstein R, Biochemistry. 2005 Mar 1;44(8):2746-58. PMID:[http:// | + | Crystal structure of lumazine synthase from Mycobacterium tuberculosis as a target for rational drug design: binding mode of a new class of purinetrione inhibitors., Morgunova E, Meining W, Illarionov B, Haase I, Jin G, Bacher A, Cushman M, Fischer M, Ladenstein R, Biochemistry. 2005 Mar 1;44(8):2746-58. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/15723519 15723519] |
[[Category: Mycobacterium tuberculosis]] | [[Category: Mycobacterium tuberculosis]] | ||
[[Category: Riboflavin synthase]] | [[Category: Riboflavin synthase]] | ||
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[[Category: x-ray diffraction]] | [[Category: x-ray diffraction]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 14:51:08 2008'' |
Revision as of 12:51, 20 March 2008
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| , resolution 2.30Å | |||||||
|---|---|---|---|---|---|---|---|
| Sites: | |||||||
| Ligands: | , , , and | ||||||
| Activity: | Riboflavin synthase, with EC number 2.5.1.9 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
LUMAZINE SYNTHASE FROM MYCOBACTERIUM TUBERCULOSIS BOUND TO 3-(1,3,7-TRIHYDRO-9-D-RIBITYL-2,6,8-PURINETRIONE-7-YL) BUTANE 1-PHOSPHATE
Overview
The enzymes involved in the biosynthesis of riboflavin represent attractive targets for the development of drugs against bacterial pathogens, because the inhibitors of these enzymes are not likely to interfere with enzymes of the mammalian metabolism. Lumazine synthase catalyzes the penultimate step in the riboflavin biosynthesis pathway. A number of substituted purinetrione compounds represent a new class of highly specific inhibitors of lumazine synthase from Mycobacterium tuberculosis. To develop potent antibiotics for the treatment of tuberculosis, we have determined the structure of lumazine synthase from M. tuberculosis in complex with two purinetrione inhibitors and have studied binding via isothermal titration calorimetry. The structures were determined by molecular replacement using lumazine synthase from Saccharomyces cerevisiae as a search model and refined at 2 and 2.3 A resolution. The R-factors were 14.7 and 17.4%, respectively, and the R(free) values were 19.3 and 26.3%, respectively. The enzyme was found to be a pentamer consisting of five subunits related by 5-fold local symmetry. The comparison of the active site architecture with the active site of previously determined lumazine synthase structures reveals a largely conserved topology with the exception of residues Gln141 and Glu136, which participate in different charge-charge interactions in the core space of the active site. The impact of structural changes in the active site on the altered binding and catalytic properties of the enzyme is discussed. Isothermal titration calorimetry measurements indicate highly specific binding of the purinetrione inhibitors to the M. tuberculosis enzyme with dissociation constants in micromolar range.
About this Structure
1W29 is a Single protein structure of sequence from Mycobacterium tuberculosis. Full crystallographic information is available from OCA.
Reference
Crystal structure of lumazine synthase from Mycobacterium tuberculosis as a target for rational drug design: binding mode of a new class of purinetrione inhibitors., Morgunova E, Meining W, Illarionov B, Haase I, Jin G, Bacher A, Cushman M, Fischer M, Ladenstein R, Biochemistry. 2005 Mar 1;44(8):2746-58. PMID:15723519
Page seeded by OCA on Thu Mar 20 14:51:08 2008
Categories: Mycobacterium tuberculosis | Riboflavin synthase | Single protein | Bacher, A. | Cushman, M. | Fischer, M. | Haase, I. | Illarionov, B. | Ladenstein, R. | Meining, W. | Morgunova, E. | ACY | D1D | K | TS0 | TS1 | Crystal structure | Inhibitor binding | Lumazine synthase | Riboflavin biosynthesis | Transferase | X-ray diffraction
