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| | <StructureSection load='6wb7' size='340' side='right'caption='[[6wb7]], [[Resolution|resolution]] 2.44Å' scene=''> | | <StructureSection load='6wb7' size='340' side='right'caption='[[6wb7]], [[Resolution|resolution]] 2.44Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6wb7]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Acts5 Acts5]. 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='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>, <scene name='pdbligand=NA:SODIUM+ION'>NA</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]] 2.44Å</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=NA:SODIUM+ION'>NA</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]], [[6wb5|6wb5]]</div></td></tr>
| + | |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">acbK, ACPL_3675 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=134676 ACTS5])</td></tr>
| + | |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Acarbose_7(IV)-phosphotransferase Acarbose 7(IV)-phosphotransferase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.187 2.7.1.187] </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=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> | | <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 == | | == 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>
| + | [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;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Acts5]] | + | [[Category: Actinoplanes sp. SE50/110]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[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
6wb7 is a 4 chain structure with sequence from Actinoplanes sp. SE50/110. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Method: | X-ray diffraction, Resolution 2.44Å |
| Ligands: | , , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
ACBK_ACTS5 Catalyzes the phosphorylation of the alpha-glucosidase inhibitor acarbose. Phosphorylation of acarbose could be a resistance-like self-protection mechanism.[1]
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[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Zhang CS, Stratmann A, Block O, Bruckner R, Podeschwa M, Altenbach HJ, Wehmeier UF, Piepersberg W. Biosynthesis of the C(7)-cyclitol moiety of acarbose in Actinoplanes species SE50/110. 7-O-phosphorylation of the initial cyclitol precursor leads to proposal of a new biosynthetic pathway. J Biol Chem. 2002 Jun 21;277(25):22853-62. doi: 10.1074/jbc.M202375200. Epub 2002, Apr 5. PMID:11937512 doi:http://dx.doi.org/10.1074/jbc.M202375200
- ↑ 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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