6i2q
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal structure of the wild-type SucA domain of Mycobacterium smegmatis KGD (alpha-ketoglutarate decarboxylase), in complex with GarA== | |
| + | <StructureSection load='6i2q' size='340' side='right'caption='[[6i2q]], [[Resolution|resolution]] 2.15Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[6i2q]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycolicibacterium_smegmatis_MC2_155 Mycolicibacterium smegmatis MC2 155]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=2xt9 2xt9]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6I2Q OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6I2Q 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]] 2.15Å</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=TPP:THIAMINE+DIPHOSPHATE'>TPP</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=6i2q FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6i2q OCA], [https://pdbe.org/6i2q PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6i2q RCSB], [https://www.ebi.ac.uk/pdbsum/6i2q PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6i2q ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/GARA_MYCS2 GARA_MYCS2] Involved in regulation of glutamate metabolism. Acts as a phosphorylation-dependent molecular switch that modulates the activities of Kgd and Gdh.<ref>PMID:19019160</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Forkhead-associated (FHA) domains are modules that bind to phosphothreonine (pThr) residues in signaling cascades. The FHA-containing mycobacterial protein GarA is a central element of a phosphorylation-dependent signaling pathway that redirects metabolic flux in response to amino acid starvation or cell growth requirements. GarA acts as a phosphorylation-dependent ON/OFF molecular switch. In its nonphosphorylated ON state, the GarA FHA domain engages in phosphorylation-independent interactions with various metabolic enzymes that orchestrate nitrogen flow, such as 2-oxoglutarate decarboxylase (KGD). However, phosphorylation at the GarA N-terminal region by the protein kinase PknB or PknG triggers autoinhibition through the intramolecular association of the N-terminal domain with the FHA domain, thus blocking all downstream interactions. To investigate these different FHA binding modes, we solved the crystal structures of the mycobacterial upstream (phosphorylation-dependent) complex PknB-GarA and the downstream (phosphorylation-independent) complex GarA-KGD. Our results show that the phosphorylated activation loop of PknB serves as a docking site to recruit GarA through canonical FHA-pThr interactions. However, the same GarA FHA-binding pocket targets an allosteric site on nonphosphorylated KGD, where a key element of recognition is a phosphomimetic aspartate. Further enzymatic and mutagenesis studies revealed that GarA acted as a dynamic allosteric inhibitor of KGD by preventing crucial motions in KGD that are necessary for catalysis. Our results provide evidence for physiological phosphomimetics, supporting numerous mutagenesis studies using such approaches, and illustrate how evolution can shape a single FHA-binding pocket to specifically interact with multiple phosphorylated and nonphosphorylated protein partners. | ||
| - | + | Structural insights into the functional versatility of an FHA domain protein in mycobacterial signaling.,Wagner T, Andre-Leroux G, Hindie V, Barilone N, Lisa MN, Hoos S, Raynal B, Vulliez-Le Normand B, O'Hare HM, Bellinzoni M, Alzari PM Sci Signal. 2019 May 7;12(580). pii: 12/580/eaav9504. doi:, 10.1126/scisignal.aav9504. PMID:31064884<ref>PMID:31064884</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: | + | <div class="pdbe-citations 6i2q" style="background-color:#fffaf0;"></div> |
| - | [[Category: Bellinzoni | + | == References == |
| - | [[Category: | + | <references/> |
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Mycolicibacterium smegmatis MC2 155]] | ||
| + | [[Category: Alzari PM]] | ||
| + | [[Category: Bellinzoni M]] | ||
| + | [[Category: Wagner T]] | ||
Current revision
Crystal structure of the wild-type SucA domain of Mycobacterium smegmatis KGD (alpha-ketoglutarate decarboxylase), in complex with GarA
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