View source for 2yid


==Crystal structure of the SucA domain of Mycobacterium smegmatis alpha- ketoglutarate decarboxylase in complex with the enamine-ThDP intermediate==
<StructureSection load='2yid' size='340' side='right'caption='[[2yid]], [[Resolution|resolution]] 2.25&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2yid]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycolicibacterium_smegmatis Mycolicibacterium smegmatis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2YID OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2YID 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]] 2.25&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=TD7:(4E)-4-{3-[(4-AMINO-2-METHYLPYRIMIDIN-5-YL)METHYL]-5-(2-{[(S)-HYDROXY(PHOSPHONOOXY)PHOSPHORYL]OXY}ETHYL)-4-METHYL-1,3-THIAZOL-2(3H)-YLIDENE}-4-HYDROXYBUTANOIC+ACID'>TD7</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=2yid FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2yid OCA], [https://pdbe.org/2yid PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2yid RCSB], [https://www.ebi.ac.uk/pdbsum/2yid PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2yid ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/KGD_MYCS2 KGD_MYCS2] Shows three enzymatic activities that share a first common step, the attack of thiamine-PP on 2-oxoglutarate (alpha-ketoglutarate, KG), leading to the formation of an enamine-thiamine-PP intermediate upon decarboxylation. Thus, displays KGD activity, catalyzing the decarboxylation from five-carbon 2-oxoglutarate to four-carbon succinate semialdehyde (SSA). Also catalyzes C-C bond formation between the activated aldehyde formed after decarboxylation of alpha-ketoglutarate and the carbonyl of glyoxylate (GLX), to yield 2-hydroxy-3-oxoadipate (HOA), which spontaneously decarboxylates to form 5-hydroxylevulinate (HLA). And is also a component of the 2-oxoglutarate dehydrogenase (ODH) complex, that catalyzes the overall conversion of 2-oxoglutarate to succinyl-CoA and CO(2). The KG decarboxylase and KG dehydrogenase reactions provide two alternative, tightly regulated, pathways connecting the oxidative and reductive branches of the TCA cycle.<ref>PMID:19019160</ref> <ref>PMID:21867916</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The alpha-ketoglutarate dehydrogenase (KDH) complex is a major regulatory point of aerobic energy metabolism. Mycobacterium tuberculosis was reported to lack KDH activity, and the putative KDH E1o component, alpha-ketoglutarate decarboxylase (KGD), was instead assigned as a decarboxylase or carboligase. Here, we show that this protein does in fact sustain KDH activity, as well as the additional two reactions, and these multifunctional properties are shared by the Escherichia coli homolog, SucA. We also show that the mycobacterial enzyme is finely regulated by an additional acyltransferase-like domain and by the action of acetyl-CoA, a powerful allosteric activator able to enhance the concerted protein motions observed during catalysis. Our results uncover the functional plasticity of a crucial node in bacterial metabolism, which may be important for M. tuberculosis during host infection.

Functional plasticity and allosteric regulation of alpha-ketoglutarate decarboxylase in central mycobacterial metabolism.,Wagner T, Bellinzoni M, Wehenkel A, O'Hare HM, Alzari PM Chem Biol. 2011 Aug 26;18(8):1011-20. PMID:21867916<ref>PMID:21867916</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 2yid" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Mycolicibacterium smegmatis]]
[[Category: Alzari PM]]
[[Category: Bellinzoni M]]
[[Category: O'Hare HM]]
[[Category: Wagner T]]
[[Category: Wehenkel AM]]