6wb4

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Current revision (11:21, 30 October 2024) (edit) (undo)
 
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<StructureSection load='6wb4' size='340' side='right'caption='[[6wb4]], [[Resolution|resolution]] 2.59&Aring;' scene=''>
<StructureSection load='6wb4' size='340' side='right'caption='[[6wb4]], [[Resolution|resolution]] 2.59&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[6wb4]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Uncultivated_bacterium Uncultivated bacterium]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6WB4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6WB4 FirstGlance]. <br>
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<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6WB4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6WB4 FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=GLC:ALPHA-D-GLUCOSE'>GLC</scene></td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.593&#8491;</td></tr>
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<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=AC1:6-METHYL-5-(4,5,6-TRIHYDROXY-3-HYDROXYMETHYL-CYCLOHEX-2-ENYLAMINO)-TETRAHYDRO-PYRAN-2,3,4-TRIOL'>AC1</scene>, <scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AC1:6-METHYL-5-(4,5,6-TRIHYDROXY-3-HYDROXYMETHYL-CYCLOHEX-2-ENYLAMINO)-TETRAHYDRO-PYRAN-2,3,4-TRIOL'>AC1</scene>, <scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=GLC:ALPHA-D-GLUCOSE'>GLC</scene>, <scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene>, <scene name='pdbligand=PRD_900007:alpha-acarbose'>PRD_900007</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=6wb4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6wb4 OCA], [https://pdbe.org/6wb4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6wb4 RCSB], [https://www.ebi.ac.uk/pdbsum/6wb4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6wb4 ProSAT]</span></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=6wb4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6wb4 OCA], [https://pdbe.org/6wb4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6wb4 RCSB], [https://www.ebi.ac.uk/pdbsum/6wb4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6wb4 ProSAT]</span></td></tr>
</table>
</table>
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<div style="background-color:#fffaf0;">
 
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== Publication Abstract from PubMed ==
 
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The human microbiome encodes a large repertoire of biochemical enzymes and pathways, most of which remain uncharacterized. Here, using a metagenomics-based search strategy, we discovered that bacterial members of the human gut and oral microbiome encode enzymes that selectively phosphorylate a clinically used antidiabetic drug, acarbose(1,2), resulting in its inactivation. Acarbose is an inhibitor of both human and bacterial alpha-glucosidases(3), limiting the ability of the target organism to metabolize complex carbohydrates. Using biochemical assays, X-ray crystallography and metagenomic analyses, we show that microbiome-derived acarbose kinases are specific for acarbose, provide their harbouring organism with a protective advantage against the activity of acarbose, and are widespread in the microbiomes of western and non-western human populations. These results provide an example of widespread microbiome resistance to a non-antibiotic drug, and suggest that acarbose resistance has disseminated in the human microbiome as a defensive strategy against a potential endogenous producer of a closely related molecule.
 
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The human microbiome encodes resistance to the antidiabetic drug acarbose.,Balaich J, Estrella M, Wu G, Jeffrey PD, Biswas A, Zhao L, Korennykh A, Donia MS Nature. 2021 Dec;600(7887):110-115. doi: 10.1038/s41586-021-04091-0. Epub 2021, Nov 24. PMID:34819672<ref>PMID:34819672</ref>
 
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 
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</div>
 
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<div class="pdbe-citations 6wb4" style="background-color:#fffaf0;"></div>
 
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== References ==
 
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<references/>
 
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Large Structures]]
[[Category: Large Structures]]
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[[Category: Uncultivated bacterium]]
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[[Category: Balaich JN]]
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[[Category: Balaich, J N]]
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[[Category: Donia MS]]
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[[Category: Donia, M S]]
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[[Category: Estrella MA]]
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[[Category: Estrella, M A]]
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[[Category: Jeffrey PD]]
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[[Category: Jeffrey, P D]]
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[[Category: Acarbose]]
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[[Category: Atp binding]]
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[[Category: Carbohydrate kinase]]
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[[Category: Complex]]
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[[Category: Metal ion binding]]
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[[Category: Nucleotide binding]]
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[[Category: Ribokinase activity]]
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[[Category: Transferase]]
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Current revision

Microbiome-derived Acarbose Kinase Mak1 Labeled with selenomethionine

PDB ID 6wb4

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