6wb7
From Proteopedia
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==Acarbose Kinase AcbK as a Complex with Acarbose and AMP-PNP== | ==Acarbose Kinase AcbK as a Complex with Acarbose and AMP-PNP== | ||
| - | <StructureSection load='6wb7' size='340' side='right'caption='[[6wb7]]' scene=''> | + | <StructureSection load='6wb7' size='340' side='right'caption='[[6wb7]], [[Resolution|resolution]] 2.44Å' 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=6WB7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6WB7 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6wb7]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Actinoplanes_sp._SE50/110 Actinoplanes sp. SE50/110]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6WB7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6WB7 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=6wb7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6wb7 OCA], [https://pdbe.org/6wb7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6wb7 RCSB], [https://www.ebi.ac.uk/pdbsum/6wb7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6wb7 ProSAT]</span></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.44Å</td></tr> |
| + | <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=ANP:PHOSPHOAMINOPHOSPHONIC+ACID-ADENYLATE+ESTER'>ANP</scene>, <scene name='pdbligand=GLC:ALPHA-D-GLUCOSE'>GLC</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</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=6wb7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6wb7 OCA], [https://pdbe.org/6wb7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6wb7 RCSB], [https://www.ebi.ac.uk/pdbsum/6wb7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6wb7 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/ACBK_ACTS5 ACBK_ACTS5] Catalyzes the phosphorylation of the alpha-glucosidase inhibitor acarbose. Phosphorylation of acarbose could be a resistance-like self-protection mechanism.<ref>PMID:11937512</ref> | ||
| + | <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®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 6wb7" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Actinoplanes sp. SE50/110]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Balaich JN]] | [[Category: Balaich JN]] | ||
Current revision
Acarbose Kinase AcbK as a Complex with Acarbose and AMP-PNP
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