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[[Image:2c94.jpg|left|200px]]


{{Structure
==LUMAZINE SYNTHASE FROM MYCOBACTERIUM TUBERCULOSIS BOUND TO 3-(1,3,7- TRIHYDRO-9-D-RIBITYL-2,6,8-PURINETRIONE-7-YL) 1,1 difluoropentane-1- PHOSPHATE==
|PDB= 2c94 |SIZE=350|CAPTION= <scene name='initialview01'>2c94</scene>, resolution 1.90&Aring;
<StructureSection load='2c94' size='340' side='right'caption='[[2c94]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
|SITE= <scene name='pdbsite=AC1:Tsf+Binding+Site+For+Chain+E'>AC1</scene>
== Structural highlights ==
|LIGAND= <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=TSF:3-(1,3,7-TRIHYDRO-9-D-RIBITYL-2,6,8-PURINETRIONE-7-YL)+1,1+DIFLUOROPENTANE-1-PHOSPHATE'>TSF</scene>
<table><tr><td colspan='2'>[[2c94]] 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=2C94 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2C94 FirstGlance]. <br>
|ACTIVITY= <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='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.9&#8491;</td></tr>
|GENE=
<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=TSF:3-(1,3,7-TRIHYDRO-9-D-RIBITYL-2,6,8-PURINETRIONE-7-YL)+1,1+DIFLUOROPENTANE-1-PHOSPHATE'>TSF</scene></td></tr>
|DOMAIN=
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2c94 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2c94 OCA], [https://pdbe.org/2c94 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2c94 RCSB], [https://www.ebi.ac.uk/pdbsum/2c94 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2c94 ProSAT]</span></td></tr>
|RELATEDENTRY=
</table>
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2c94 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2c94 OCA], [http://www.ebi.ac.uk/pdbsum/2c94 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2c94 RCSB]</span>
== 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>
 
== Evolutionary Conservation ==
'''LUMAZINE SYNTHASE FROM MYCOBACTERIUM TUBERCULOSIS BOUND TO 3-(1,3,7-TRIHYDRO-9-D-RIBITYL-2,6,8-PURINETRIONE-7-YL) 1,1 DIFLUOROPENTANE-1-PHOSPHATE'''
[[Image:Consurf_key_small.gif|200px|right]]
 
Check<jmol>
 
  <jmolCheckbox>
==Overview==
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/c9/2c94_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</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=2c94 ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
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.
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==
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>
2C94 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=2C94 OCA].


==Reference==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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://www.ncbi.nlm.nih.gov/pubmed/16984393 16984393]
</div>
<div class="pdbe-citations 2c94" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Mycobacterium tuberculosis]]
[[Category: Mycobacterium tuberculosis]]
[[Category: Riboflavin synthase]]
[[Category: Bacher A]]
[[Category: Single protein]]
[[Category: Cushman M]]
[[Category: Bacher, A.]]
[[Category: Fischer M]]
[[Category: Cushman, M.]]
[[Category: Haase I]]
[[Category: Fischer, M.]]
[[Category: Illarionov B]]
[[Category: Haase, I.]]
[[Category: Jin G]]
[[Category: Illarionov, B.]]
[[Category: Ladenstein R]]
[[Category: Jin, G.]]
[[Category: Morgunova E]]
[[Category: Ladenstein, R.]]
[[Category: Morgunova, E.]]
[[Category: transferase,riboflavin biosynthesis,mycobacterium tuberculosis,lumazine synthase,inhibitor binding]]
 
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