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| | <StructureSection load='6wb5' size='340' side='right'caption='[[6wb5]], [[Resolution|resolution]] 3.10Å' scene=''> | | <StructureSection load='6wb5' size='340' side='right'caption='[[6wb5]], [[Resolution|resolution]] 3.10Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6wb5]] 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=6WB5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6WB5 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6wb5]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Uncultured_bacterium Uncultured bacterium]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6WB5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6WB5 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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></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]] 3.102Å</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></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=PRD_900007:alpha-acarbose'>PRD_900007</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[6wb4|6wb4]]</div></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=6wb5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6wb5 OCA], [https://pdbe.org/6wb5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6wb5 RCSB], [https://www.ebi.ac.uk/pdbsum/6wb5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6wb5 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=6wb5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6wb5 OCA], [https://pdbe.org/6wb5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6wb5 RCSB], [https://www.ebi.ac.uk/pdbsum/6wb5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6wb5 ProSAT]</span></td></tr> |
| | </table> | | </table> |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Uncultivated bacterium]] | + | [[Category: Uncultured bacterium]] |
| - | [[Category: Balaich, J N]] | + | [[Category: Balaich JN]] |
| - | [[Category: Donia, M S]] | + | [[Category: Donia MS]] |
| - | [[Category: Estrella, M A]] | + | [[Category: Estrella MA]] |
| - | [[Category: Jeffrey, P D]] | + | [[Category: Jeffrey PD]] |
| - | [[Category: Acarbose]]
| + | |
| - | [[Category: Atp binding]]
| + | |
| - | [[Category: Carbohydrate kinase]]
| + | |
| - | [[Category: Complex]]
| + | |
| - | [[Category: Metal ion binding]]
| + | |
| - | [[Category: Nucleotide binding]]
| + | |
| - | [[Category: Ribokinase activity]]
| + | |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
6wb5 is a 2 chain structure with sequence from Uncultured bacterium. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Method: | X-ray diffraction, Resolution 3.102Å |
| Ligands: | , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
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[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Balaich J, Estrella M, Wu G, Jeffrey PD, Biswas A, Zhao L, Korennykh A, Donia MS. The human microbiome encodes resistance to the antidiabetic drug acarbose. Nature. 2021 Dec;600(7887):110-115. doi: 10.1038/s41586-021-04091-0. Epub 2021, Nov 24. PMID:34819672 doi:http://dx.doi.org/10.1038/s41586-021-04091-0
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