2c9b

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[[Image:2c9b.gif|left|200px]]<br />
 
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<applet load="2c9b" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="2c9b, resolution 2.75&Aring;" />
 
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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)'''<br />
 
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==Overview==
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==Lumazine Synthase from Mycobacterium tuberculosus Bound to 3-(1,3,7- TRIHYDRO-9-D-RIBITYL-2,6,8-PURINETRIONE-7-YL)==
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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.
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<StructureSection load='2c9b' size='340' side='right'caption='[[2c9b]], [[Resolution|resolution]] 2.75&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[2c9b]] 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=2C9B OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2C9B FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.75&#8491;</td></tr>
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<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=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=PUG:3-(1,3,7-TRIHYDRO-9-D-RIBITYL-2,6,8-PURINETRIONE-7-YL)'>PUG</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2c9b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2c9b OCA], [https://pdbe.org/2c9b PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2c9b RCSB], [https://www.ebi.ac.uk/pdbsum/2c9b PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2c9b ProSAT]</span></td></tr>
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</table>
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== Function ==
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[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>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/c9/2c9b_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2c9b ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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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.
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==About this Structure==
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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<ref>PMID:16984393</ref>
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2C9B 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, PO4, PUG 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=2C9B OCA].
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==Reference==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=16984393 16984393]
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</div>
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<div class="pdbe-citations 2c9b" style="background-color:#fffaf0;"></div>
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== References ==
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Large Structures]]
[[Category: Mycobacterium tuberculosis]]
[[Category: Mycobacterium tuberculosis]]
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[[Category: Riboflavin synthase]]
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[[Category: Bacher A]]
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[[Category: Single protein]]
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[[Category: Cushman M]]
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[[Category: Bacher, A.]]
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[[Category: Fischer M]]
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[[Category: Cushman, M.]]
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[[Category: Haase I]]
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[[Category: Fischer, M.]]
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[[Category: Illarionov B]]
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[[Category: Haase, I.]]
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[[Category: Jin G]]
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[[Category: Illarionov, B.]]
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[[Category: Ladenstein R]]
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[[Category: Jin, G.]]
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[[Category: Morgunova E]]
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[[Category: Ladenstein, R.]]
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[[Category: Morgunova, E.]]
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[[Category: K]]
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[[Category: MPD]]
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[[Category: PO4]]
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[[Category: PUG]]
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[[Category: inhibitor binding]]
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[[Category: lumazine synthase]]
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[[Category: mycobacterium tuberculosis]]
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[[Category: riboflavin biosynthesis]]
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[[Category: transferase]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 5 18:03:06 2007''
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Current revision

Lumazine Synthase from Mycobacterium tuberculosus Bound to 3-(1,3,7- TRIHYDRO-9-D-RIBITYL-2,6,8-PURINETRIONE-7-YL)

PDB ID 2c9b

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