6WB5

Microbiome-derived Acarbose Kinase Mak1 as a Complex with Acarbose and AMP-PNP

6WB5 の概要

• エントリーDOI: 10.2210/pdb6wb5/pdb
• 関連するPDBエントリー: 6WB4
• 関連するBIRD辞書のPRD_ID: PRD_900007
• 分子名称: Acarbose Kinase Mak1, 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, ... (4 entities in total)
• 機能のキーワード: carbohydrate kinase, acarbose, transferase, nucleotide binding, atp binding, metal ion binding, ribokinase activity, complex
• 由来する生物種: uncultured bacterium
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 70800.48

構造登録者

Jeffrey, P.D.,Balaich, J.N.,Estrella, M.A.,Donia, M.S. (登録日: 2020-03-26, 公開日: 2021-04-21, 最終更新日: 2023-10-18)

主引用文献

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

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: 34819672
DOI: 10.1038/s41586-021-04091-0

実験手法

X-RAY DIFFRACTION (3.102 Å)