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==Microbiome-derived Acarbose Kinase Mak1 Labeled with selenomethionine==
==Microbiome-derived Acarbose Kinase Mak1 Labeled with selenomethionine==
<StructureSection load='6wb4' size='340' side='right'caption='[[6wb4]]' scene=''>
<StructureSection load='6wb4' size='340' side='right'caption='[[6wb4]], [[Resolution|resolution]] 2.59&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<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>
<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>
</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>
</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>
<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>
<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>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
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.
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>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6wb4" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Balaich JN]]
[[Category: Uncultivated bacterium]]
[[Category: Donia MS]]
[[Category: Balaich, J N]]
[[Category: Estrella MA]]
[[Category: Donia, M S]]
[[Category: Jeffrey PD]]
[[Category: Estrella, M A]]
[[Category: Jeffrey, P D]]
[[Category: Acarbose]]
[[Category: Atp binding]]
[[Category: Carbohydrate kinase]]
[[Category: Complex]]
[[Category: Metal ion binding]]
[[Category: Nucleotide binding]]
[[Category: Ribokinase activity]]
[[Category: Transferase]]
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