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| | <StructureSection load='1w29' size='340' side='right'caption='[[1w29]], [[Resolution|resolution]] 2.30Å' scene=''> | | <StructureSection load='1w29' size='340' side='right'caption='[[1w29]], [[Resolution|resolution]] 2.30Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1w29]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/"bacillus_tuberculosis"_(zopf_1883)_klein_1884 "bacillus tuberculosis" (zopf 1883) klein 1884]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1W29 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1W29 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1w29]] is a 5 chain structure with sequence from [https://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]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1W29 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACY:ACETIC+ACID'>ACY</scene>, <scene name='pdbligand=D1D:(4S,5S)-1,2-DITHIANE-4,5-DIOL'>D1D</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</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=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></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1w19|1w19]]</div></td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACY:ACETIC+ACID'>ACY</scene>, <scene name='pdbligand=D1D:(4S,5S)-1,2-DITHIANE-4,5-DIOL'>D1D</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</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=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></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Riboflavin_synthase Riboflavin synthase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.5.1.9 2.5.1.9] </span></td></tr>
| + | |
| | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1w29 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1w29 OCA], [https://pdbe.org/1w29 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1w29 RCSB], [https://www.ebi.ac.uk/pdbsum/1w29 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1w29 ProSAT]</span></td></tr> | | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1w29 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1w29 OCA], [https://pdbe.org/1w29 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1w29 RCSB], [https://www.ebi.ac.uk/pdbsum/1w29 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1w29 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/RISB_MYCTU 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.<ref>PMID:15723519</ref>
| + | [https://www.uniprot.org/uniprot/RISB_MYCTU 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.<ref>PMID:15723519</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Riboflavin synthase]] | + | [[Category: Mycobacterium tuberculosis]] |
| - | [[Category: Bacher, A]] | + | [[Category: Bacher A]] |
| - | [[Category: Cushman, M]] | + | [[Category: Cushman M]] |
| - | [[Category: Fischer, M]] | + | [[Category: Fischer M]] |
| - | [[Category: Haase, I]] | + | [[Category: Haase I]] |
| - | [[Category: Illarionov, B]] | + | [[Category: Illarionov B]] |
| - | [[Category: Ladenstein, R]] | + | [[Category: Ladenstein R]] |
| - | [[Category: Meining, W]] | + | [[Category: Meining W]] |
| - | [[Category: Morgunova, E]] | + | [[Category: Morgunova E]] |
| - | [[Category: Inhibitor binding]]
| + | |
| - | [[Category: Lumazine synthase]]
| + | |
| - | [[Category: Riboflavin biosynthesis]]
| + | |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
1w29 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 2.3Å |
| 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.[1]
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
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.
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[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Morgunova E, Meining W, Illarionov B, Haase I, Jin G, Bacher A, Cushman M, Fischer M, Ladenstein R. Crystal structure of lumazine synthase from Mycobacterium tuberculosis as a target for rational drug design: binding mode of a new class of purinetrione inhibitors. Biochemistry. 2005 Mar 1;44(8):2746-58. PMID:15723519 doi:10.1021/bi047848a
- ↑ Morgunova E, Meining W, Illarionov B, Haase I, Jin G, Bacher A, Cushman M, Fischer M, Ladenstein R. Crystal structure of lumazine synthase from Mycobacterium tuberculosis as a target for rational drug design: binding mode of a new class of purinetrione inhibitors. Biochemistry. 2005 Mar 1;44(8):2746-58. PMID:15723519 doi:10.1021/bi047848a
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