9obo: Difference between revisions

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~~'''Unreleased structure'''~~

~~The entry~~ 9obo is ~~ON HOLD~~

==Crystal structure of Mycobacterium tuberculosis isocitrate lyase 2 fixed in the apo form with disulfide bonds==

== Structural highlights ==

<table><tr><td colspan='2'>[[9obo]] 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=9OBO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9OBO FirstGlance]. <br>

</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.6Å</td></tr>

<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=SIN:SUCCINIC+ACID'>SIN</scene></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=9obo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9obo OCA], [https://pdbe.org/9obo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9obo RCSB], [https://www.ebi.ac.uk/pdbsum/9obo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9obo ProSAT]</span></td></tr>

</table>

== Function ==

[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>

== Publication Abstract from PubMed ==

Mycobacterium tuberculosis isocitrate lyase 2 (ICL2) is an allosterically regulated enzyme required for growth on non-glycolytic carbon substrates during infection. Although acetyl-CoA and its analogues are known to activate ICL2, the molecular basis of this regulation has remained unclear. Here, we combine protein NMR, crystallography, molecular dynamics, and mutagenesis to show that two structural features unique to ICL2, the C-terminal domain and a helical substructure in the N-terminal catalytic domain, govern its allostery. Acetyl-CoA binding promotes dimerisation of the C-terminal domain and disrupts its contacts with the helical substructure to trigger conformational changes that activate the enzyme. Together, these findings reveal how a non-substrate metabolite drives isocitrate lyase activation, uncovering the allosteric mechanism that controls M. tuberculosis metabolism and informs new therapeutic strategies.

~~Authors~~:

Structural basis of allosteric activation of Mycobacterium tuberculosis isocitrate lyase 2.,Huang EY, Kwai BXC, Jiao W, Taka J, Wilde KL, Sethi A, Maher MJ, Bashiri G, Leung IKH Commun Biol. 2026 Mar 9. doi: 10.1038/s42003-026-09821-6. PMID:41803459<ref>PMID:41803459</ref>

~~Description~~:

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>

[[Category: ~~Unreleased~~ Structures]]

</div>

== References ==

__TOC__

</StructureSection>

[[Category: Large Structures]]

[[Category: Mycobacterium tuberculosis CDC1551]]

[[Category: Huang EYW]]

[[Category: Leung IKH]]

[[Category: Maher MJ]]

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@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 9obo is ON HOLD
+==Crystal structure of Mycobacterium tuberculosis isocitrate lyase 2 fixed in the apo form with disulfide bonds==
+<StructureSection load='9obo' size='340' side='right'caption='[[9obo]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[9obo]] 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=9OBO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9OBO FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.6&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=SIN:SUCCINIC+ACID'>SIN</scene></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=9obo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9obo OCA], [https://pdbe.org/9obo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9obo RCSB], [https://www.ebi.ac.uk/pdbsum/9obo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9obo ProSAT]</span></td></tr>
+</table>
+== Function ==
+[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;">
+== Publication Abstract from PubMed ==
+Mycobacterium tuberculosis isocitrate lyase 2 (ICL2) is an allosterically regulated enzyme required for growth on non-glycolytic carbon substrates during infection. Although acetyl-CoA and its analogues are known to activate ICL2, the molecular basis of this regulation has remained unclear. Here, we combine protein NMR, crystallography, molecular dynamics, and mutagenesis to show that two structural features unique to ICL2, the C-terminal domain and a helical substructure in the N-terminal catalytic domain, govern its allostery. Acetyl-CoA binding promotes dimerisation of the C-terminal domain and disrupts its contacts with the helical substructure to trigger conformational changes that activate the enzyme. Together, these findings reveal how a non-substrate metabolite drives isocitrate lyase activation, uncovering the allosteric mechanism that controls M. tuberculosis metabolism and informs new therapeutic strategies.
-Authors:
+Structural basis of allosteric activation of Mycobacterium tuberculosis isocitrate lyase 2.,Huang EY, Kwai BXC, Jiao W, Taka J, Wilde KL, Sethi A, Maher MJ, Bashiri G, Leung IKH Commun Biol. 2026 Mar 9. doi: 10.1038/s42003-026-09821-6. PMID:41803459<ref>PMID:41803459</ref>
-Description:
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
+<div class="pdbe-citations 9obo" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Large Structures]]
+[[Category: Mycobacterium tuberculosis CDC1551]]
+[[Category: Huang EYW]]
+[[Category: Leung IKH]]
+[[Category: Maher MJ]]