6wb7
Acarbose Kinase AcbK as a Complex with Acarbose and AMP-PNP
Structural highlights
FunctionACBK_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 PubMedThe 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
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