6WB7
Acarbose Kinase AcbK as a Complex with Acarbose and AMP-PNP
Summary for 6WB7
| Entry DOI | 10.2210/pdb6wb7/pdb |
| Related | 6WB4 6WB5 |
| Related PRD ID | PRD_900007 |
| Descriptor | Acarbose 7(IV)-phosphotransferase, 4,6-dideoxy-4-{[(1S,4R,5S,6S)-4,5,6-trihydroxy-3-(hydroxymethyl)cyclohex-2-en-1-yl]amino}-alpha-D-glucopyranose-(1-4)-alpha-D-glucopyranose-(1-4)-alpha-D-glucopyranose, PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER, ... (6 entities in total) |
| Functional Keywords | carbohydrate kinase, acarbose, transferase, nucleotide binding, atp binding, metal ion binding, ribokinase activity, complex |
| Biological source | Actinoplanes sp. (strain ATCC 31044 / CBS 674.73 / SE50/110) |
| Total number of polymer chains | 4 |
| Total formula weight | 139721.05 |
| Authors | Jeffrey, P.D.,Balaich, J.N.,Estrella, M.A.,Donia, M.S. (deposition date: 2020-03-26, release date: 2021-04-21, Last modification date: 2023-10-18) |
| Primary citation | Balaich, J.,Estrella, M.,Wu, G.,Jeffrey, P.D.,Biswas, A.,Zhao, L.,Korennykh, A.,Donia, M.S. The human microbiome encodes resistance to the antidiabetic drug acarbose. Nature, 600:110-115, 2021 Cited by PubMed Abstract: 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, resulting in its inactivation. Acarbose is an inhibitor of both human and bacterial α-glucosidases, 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. PubMed: 34819672DOI: 10.1038/s41586-021-04091-0 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.44 Å) |
Structure validation
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