6wb4 | pdb_00006wb4

Microbiome-derived Acarbose Kinase Mak1 Labeled with selenomethionine

spinqualitylabelsall models 6wb4, resolution 2.59Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6wb4 is a 2 chain structure with sequence from Uncultivated bacterium. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: ATP, CA, GLC NonStd Res: AC1, MSE 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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