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6edz

From Proteopedia

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Current revision

Crystal structure of Mycobacterium tuberculosis ICL2 in complex with acetyl-CoA, form I

Structural highlights

6edz is a 4 chain structure with sequence from Mycto. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
NonStd Res:
Related:	6edw, 6ee1
Gene:	icl2, aceA-2, MT1966 (MYCTO)
Activity:	Isocitrate lyase, with EC number 4.1.3.1
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6edz"

@@ Line 3: / Line 3: @@
 <StructureSection load='6edz' size='340' side='right'caption='[[6edz]], [[Resolution|resolution]] 2.67&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6edz]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6EDZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6EDZ FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6edz]] 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=6EDZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6EDZ FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACO:ACETYL+COENZYME+*A'>ACO</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">[[6edw|6edw]], [[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=6edz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6edz OCA], [http://pdbe.org/6edz PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6edz RCSB], [http://www.ebi.ac.uk/pdbsum/6edz PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6edz ProSAT]</span></td></tr>
@@ Line 12: / Line 13: @@
 == 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&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 6edz" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>
@@ Line 18: / Line 28: @@
 [[Category: Isocitrate lyase]]
 [[Category: Large Structures]]
+[[Category: Mycto]]
 [[Category: Bashiri, G]]
 [[Category: Bhusal, R]]
 [[Category: Leung, I]]
 [[Category: Lyase]]

6edz

From Proteopedia

Current revision

Crystal structure of Mycobacterium tuberculosis ICL2 in complex with acetyl-CoA, form I

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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