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==Crystal structure of Mycobacterium tuberculosis ICL2 in the apo form== | |||
<StructureSection load='6edw' size='340' side='right'caption='[[6edw]], [[Resolution|resolution]] 1.80Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6edw]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Mycto Mycto]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6EDW OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6EDW FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr> | |||
<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CSX:S-OXY+CYSTEINE'>CSX</scene></td></tr> | |||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6edz|6edz]], [[6ee1|6ee1]]</td></tr> | |||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">icl2, aceA-2, MT1966 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83331 MYCTO])</td></tr> | |||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Isocitrate_lyase Isocitrate lyase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.1.3.1 4.1.3.1] </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=6edw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6edw OCA], [http://pdbe.org/6edw PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6edw RCSB], [http://www.ebi.ac.uk/pdbsum/6edw PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6edw ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[[http://www.uniprot.org/uniprot/ACEA2_MYCTO ACEA2_MYCTO]] Involved in the persistence and virulence of M.tuberculosis. Catalyzes the reversible formation of succinate and glyoxylate from isocitrate, a key step of the glyoxylate cycle, which operates as an anaplerotic route for replenishing the tricarboxylic acid cycle during growth on fatty acid substrates.<ref>PMID:10572116</ref> <ref>PMID:15895072</ref> <ref>PMID:16879647</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Isocitrate lyase is important for lipid utilisation by Mycobacterium tuberculosis but its ICL2 isoform is poorly understood. Here we report that binding of the lipid metabolites acetyl-CoA or propionyl-CoA to ICL2 induces a striking structural rearrangement, substantially increasing isocitrate lyase and methylisocitrate lyase activities. Thus, ICL2 plays a pivotal role regulating carbon flux between the tricarboxylic acid (TCA) cycle, glyoxylate shunt and methylcitrate cycle at high lipid concentrations, a mechanism essential for bacterial growth and virulence. | |||
Acetyl-CoA-mediated activation of Mycobacterium tuberculosis isocitrate lyase 2.,Bhusal RP, Jiao W, Kwai BXC, Reynisson J, Collins AJ, Sperry J, Bashiri G, Leung IKH Nat Commun. 2019 Oct 11;10(1):4639. doi: 10.1038/s41467-019-12614-7. PMID:31604954<ref>PMID:31604954</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 6edw" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Isocitrate lyase]] | |||
[[Category: Large Structures]] | |||
[[Category: Mycto]] | |||
[[Category: Bashiri, G]] | |||
[[Category: Bhusal, R]] | |||
[[Category: Leung, I]] | |||
[[Category: Lyase]] | |||
Latest revision as of 10:50, 23 October 2019
Crystal structure of Mycobacterium tuberculosis ICL2 in the apo formCrystal structure of Mycobacterium tuberculosis ICL2 in the apo form
Structural highlights
Function[ACEA2_MYCTO] Involved in the persistence and virulence of M.tuberculosis. Catalyzes the reversible formation of succinate and glyoxylate from isocitrate, a key step of the glyoxylate cycle, which operates as an anaplerotic route for replenishing the tricarboxylic acid cycle during growth on fatty acid substrates.[1] [2] [3] Publication Abstract from PubMedIsocitrate lyase is important for lipid utilisation by Mycobacterium tuberculosis but its ICL2 isoform is poorly understood. Here we report that binding of the lipid metabolites acetyl-CoA or propionyl-CoA to ICL2 induces a striking structural rearrangement, substantially increasing isocitrate lyase and methylisocitrate lyase activities. Thus, ICL2 plays a pivotal role regulating carbon flux between the tricarboxylic acid (TCA) cycle, glyoxylate shunt and methylcitrate cycle at high lipid concentrations, a mechanism essential for bacterial growth and virulence. Acetyl-CoA-mediated activation of Mycobacterium tuberculosis isocitrate lyase 2.,Bhusal RP, Jiao W, Kwai BXC, Reynisson J, Collins AJ, Sperry J, Bashiri G, Leung IKH Nat Commun. 2019 Oct 11;10(1):4639. doi: 10.1038/s41467-019-12614-7. PMID:31604954[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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