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| | <StructureSection load='6edw' size='340' side='right'caption='[[6edw]], [[Resolution|resolution]] 1.80Å' scene=''> | | <StructureSection load='6edw' size='340' side='right'caption='[[6edw]], [[Resolution|resolution]] 1.80Å' scene=''> |
| | == Structural highlights == | | == 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> | + | <table><tr><td colspan='2'>[[6edw]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis_CDC1551 Mycobacterium tuberculosis CDC1551]. 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 [https://proteopedia.org/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> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.8Å</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='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CSX:S-OXY+CYSTEINE'>CSX</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6edw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6edw OCA], [https://pdbe.org/6edw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6edw RCSB], [https://www.ebi.ac.uk/pdbsum/6edw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6edw ProSAT]</span></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> | | </table> |
| | == Function == | | == 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> | + | [https://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;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Isocitrate lyase]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Mycto]] | + | [[Category: Mycobacterium tuberculosis CDC1551]] |
| - | [[Category: Bashiri, G]] | + | [[Category: Bashiri G]] |
| - | [[Category: Bhusal, R]] | + | [[Category: Bhusal R]] |
| - | [[Category: Leung, I]] | + | [[Category: Leung I]] |
| - | [[Category: Lyase]]
| + | |
| 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 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[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Honer Zu Bentrup K, Miczak A, Swenson DL, Russell DG. Characterization of activity and expression of isocitrate lyase in Mycobacterium avium and Mycobacterium tuberculosis. J Bacteriol. 1999 Dec;181(23):7161-7. PMID:10572116
- ↑ Munoz-Elias EJ, McKinney JD. Mycobacterium tuberculosis isocitrate lyases 1 and 2 are jointly required for in vivo growth and virulence. Nat Med. 2005 Jun;11(6):638-44. doi: 10.1038/nm1252. Epub 2005 May 15. PMID:15895072 doi:http://dx.doi.org/10.1038/nm1252
- ↑ Gould TA, van de Langemheen H, Munoz-Elias EJ, McKinney JD, Sacchettini JC. Dual role of isocitrate lyase 1 in the glyoxylate and methylcitrate cycles in Mycobacterium tuberculosis. Mol Microbiol. 2006 Aug;61(4):940-7. doi: 10.1111/j.1365-2958.2006.05297.x. PMID:16879647 doi:http://dx.doi.org/10.1111/j.1365-2958.2006.05297.x
- ↑ Bhusal RP, Jiao W, Kwai BXC, Reynisson J, Collins AJ, Sperry J, Bashiri G, Leung IKH. Acetyl-CoA-mediated activation of Mycobacterium tuberculosis isocitrate lyase 2. Nat Commun. 2019 Oct 11;10(1):4639. doi: 10.1038/s41467-019-12614-7. PMID:31604954 doi:http://dx.doi.org/10.1038/s41467-019-12614-7
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