2y0p

From Proteopedia

(Difference between revisions)

Revision as of 12:29, 22 July 2020

Crystal structure of the SucA domain of Mycobacterium smegmatis alpha- ketoglutarate decarboxylase in complex with the enamine-ThDP intermediate and acetyl-CoA

Structural highlights

2y0p is a 4 chain structure with sequence from Mycs2. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, ,
Related:	2xt5, 2xt8, 2xta, 2xt7, 2xt9, 2xt6
Activity:	2-oxoglutarate decarboxylase, with EC number 4.1.1.71
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[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.^[1] ^[2]

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^[3]

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

References

↑ O'Hare HM, Duran R, Cervenansky C, Bellinzoni M, Wehenkel AM, Pritsch O, Obal G, Baumgartner J, Vialaret J, Johnsson K, Alzari PM. Regulation of glutamate metabolism by protein kinases in mycobacteria. Mol Microbiol. 2008 Dec;70(6):1408-23. doi: 10.1111/j.1365-2958.2008.06489.x., Epub 2008 Oct 17. PMID:19019160 doi:http://dx.doi.org/10.1111/j.1365-2958.2008.06489.x
↑ Wagner T, Bellinzoni M, Wehenkel A, O'Hare HM, Alzari PM. Functional plasticity and allosteric regulation of alpha-ketoglutarate decarboxylase in central mycobacterial metabolism. Chem Biol. 2011 Aug 26;18(8):1011-20. PMID:21867916 doi:10.1016/j.chembiol.2011.06.004
↑ Wagner T, Bellinzoni M, Wehenkel A, O'Hare HM, Alzari PM. Functional plasticity and allosteric regulation of alpha-ketoglutarate decarboxylase in central mycobacterial metabolism. Chem Biol. 2011 Aug 26;18(8):1011-20. PMID:21867916 doi:10.1016/j.chembiol.2011.06.004

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/2y0p"

@@ Line 1: / Line 1: @@
 ==Crystal structure of the SucA domain of Mycobacterium smegmatis alpha- ketoglutarate decarboxylase in complex with the enamine-ThDP intermediate and acetyl-CoA==
-<StructureSection load='2y0p' size='340' side='right' caption='[[2y0p]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
+<StructureSection load='2y0p' size='340' side='right'caption='[[2y0p]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2y0p]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Mycs2 Mycs2]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2Y0P OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2Y0P FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2y0p]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Mycs2 Mycs2]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2Y0P OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=2Y0P 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>, <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>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACO:ACETYL+COENZYME+*A'>ACO</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='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2xt5|2xt5]], [[2xt8|2xt8]], [[2xta|2xta]], [[2xt7|2xt7]], [[2xt9|2xt9]], [[2xt6|2xt6]]</td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/2-oxoglutarate_decarboxylase 2-oxoglutarate decarboxylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.1.1.71 4.1.1.71] </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=2y0p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2y0p OCA], [http://pdbe.org/2y0p PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2y0p RCSB], [http://www.ebi.ac.uk/pdbsum/2y0p PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2y0p ProSAT]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=2y0p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2y0p OCA], [http://pdbe.org/2y0p PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2y0p RCSB], [http://www.ebi.ac.uk/pdbsum/2y0p PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2y0p ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 25: / Line 25: @@
 </StructureSection>
 [[Category: 2-oxoglutarate decarboxylase]]
+[[Category: Large Structures]]
 [[Category: Mycs2]]
 [[Category: Alzari, P M]]

2y0p

From Proteopedia

Revision as of 12:29, 22 July 2020

Crystal structure of the SucA domain of Mycobacterium smegmatis alpha- ketoglutarate decarboxylase in complex with the enamine-ThDP intermediate and acetyl-CoA

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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