|
|
| (2 intermediate revisions not shown.) |
| Line 1: |
Line 1: |
| | | | |
| | ==LUMAZINE SYNTHASE FROM MYCOBACTERIUM TUBERCULOSIS BOUND TO N-6-(ribitylamino)pyrimidine-2,4(1H,3H)-dione-5-yl-propionamide== | | ==LUMAZINE SYNTHASE FROM MYCOBACTERIUM TUBERCULOSIS BOUND TO N-6-(ribitylamino)pyrimidine-2,4(1H,3H)-dione-5-yl-propionamide== |
| - | <StructureSection load='2vi5' size='340' side='right' caption='[[2vi5]], [[Resolution|resolution]] 2.30Å' scene=''> | + | <StructureSection load='2vi5' size='340' side='right'caption='[[2vi5]], [[Resolution|resolution]] 2.30Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2vi5]] is a 10 chain structure with sequence from [http://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=2VI5 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2VI5 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2vi5]] is a 10 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=2VI5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2VI5 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=Y19:1-DEOXY-1-{[(5S)-2,6-DIOXO-5-(PROPANOYLAMINO)-1,2,5,6-TETRAHYDROPYRIMIDIN-4-YL]AMINO}-D-RIBITOL'>Y19</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">[[2c92|2c92]], [[2c97|2c97]], [[2c9d|2c9d]], [[1w19|1w19]], [[1w29|1w29]], [[2c94|2c94]], [[2c9b|2c9b]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=Y19:1-DEOXY-1-{[(5S)-2,6-DIOXO-5-(PROPANOYLAMINO)-1,2,5,6-TETRAHYDROPYRIMIDIN-4-YL]AMINO}-D-RIBITOL'>Y19</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[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] </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=2vi5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2vi5 OCA], [https://pdbe.org/2vi5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2vi5 RCSB], [https://www.ebi.ac.uk/pdbsum/2vi5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2vi5 ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2vi5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2vi5 OCA], [http://pdbe.org/2vi5 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2vi5 RCSB], [http://www.ebi.ac.uk/pdbsum/2vi5 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2vi5 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://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]] |
| Line 34: |
Line 33: |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Riboflavin synthase]] | + | [[Category: Large Structures]] |
| - | [[Category: Bacher, A]]
| + | |
| - | [[Category: Cushman, M]]
| + | |
| - | [[Category: Fischer, M]]
| + | |
| - | [[Category: Illarionov, B]]
| + | |
| - | [[Category: Jin, G]]
| + | |
| - | [[Category: Ladenstein, R]]
| + | |
| - | [[Category: Morgunova, E]]
| + | |
| - | [[Category: Zhang, Y]]
| + | |
| - | [[Category: Lumazine synthase]]
| + | |
| | [[Category: Mycobacterium tuberculosis]] | | [[Category: Mycobacterium tuberculosis]] |
| - | [[Category: Riboflavin biosynthesis]] | + | [[Category: Bacher A]] |
| - | [[Category: Transferase]] | + | [[Category: Cushman M]] |
| | + | [[Category: Fischer M]] |
| | + | [[Category: Illarionov B]] |
| | + | [[Category: Jin G]] |
| | + | [[Category: Ladenstein R]] |
| | + | [[Category: Morgunova E]] |
| | + | [[Category: Zhang Y]] |
| Structural highlights
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 penultimate step in the biosynthesis of riboflavin is catalyzed by lumazine synthase. Three metabolically stable analogues of the hypothetical intermediate proposed to arise after phosphate elimination in the lumazine synthase-catalyzed reaction were synthesized and evaluated as lumazine synthase inhibitors. All three intermediate analogues were inhibitors of Mycobacterium tuberculosis lumazine synthase, Bacillus subtilis lumazine synthase, and Schizosaccharomyces pombe lumazine synthase, while one of them proved to be an extremely potent inhibitor of Escherichia coli riboflavin synthase with a Ki of 1.3 nM. The crystal structure of M. tuberculosis lumazine synthase in complex with one of the inhibitors provides a model of the conformation of the intermediate occurring immediately after phosphate elimination, supporting a mechanism in which phosphate elimination occurs before a conformational change of the Schiff base intermediate toward a cyclic structure.
A New Series of N-[2,4-Dioxo-6-d-ribitylamino-1,2,3,4-tetrahydropyrimidin-5-yl]oxalamic Acid Derivatives as Inhibitors of Lumazine Synthase and Riboflavin Synthase: Design, Synthesis, Biochemical Evaluation, Crystallography, and Mechanistic Implications.,Zhang Y, Illarionov B, Morgunova E, Jin G, Bacher A, Fischer M, Ladenstein R, Cushman M J Org Chem. 2008 Apr 4;73(7):2715-2724. Epub 2008 Mar 11. PMID:18331058[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
- ↑ Zhang Y, Illarionov B, Morgunova E, Jin G, Bacher A, Fischer M, Ladenstein R, Cushman M. A New Series of N-[2,4-Dioxo-6-d-ribitylamino-1,2,3,4-tetrahydropyrimidin-5-yl]oxalamic Acid Derivatives as Inhibitors of Lumazine Synthase and Riboflavin Synthase: Design, Synthesis, Biochemical Evaluation, Crystallography, and Mechanistic Implications. J Org Chem. 2008 Apr 4;73(7):2715-2724. Epub 2008 Mar 11. PMID:18331058 doi:10.1021/jo702631a
|
