8RYI

Metformin hydrolase from Aminobacter niigataensis MD1 with urea in the active site

8RYI の概要

• エントリーDOI: 10.2210/pdb8ryi/pdb
• 分子名称: Arginase family protein, Agmatinase family protein, dicarbonimidic diamide, ... (7 entities in total)
• 機能のキーワード: metformin hydrolase, ureohydrolase, nickel-dependent, metal binding protein
• 由来する生物種: Aminobacter niigataensis; 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 236979.49

構造登録者

Fleming, J.R.,Lutz, H.,Bachmann, A.,Mayans, O. (登録日: 2024-02-08, 公開日: 2024-08-28, 最終更新日: 2024-10-02)

主引用文献

Sinn, M.,Riede, L.,Fleming, J.R.,Funck, D.,Lutz, H.,Bachmann, A.,Mayans, O.,Hartig, J.S.
Metformin hydrolase is a recently evolved nickel-dependent heteromeric ureohydrolase.
Nat Commun, 15:8045-8045, 2024

PubMed Abstract: The anti-diabetic drug metformin is one of the most widely prescribed medicines in the world. Together with its degradation product guanylurea, it is a major pharmaceutical pollutant in wastewater treatment plants and surface waters. An operon comprising two genes of the ureohydrolase family in Pseudomonas and Aminobacter species has recently been implicated in metformin degradation. However, the corresponding proteins have not been characterized. Here we show that these genes encode a Ni-dependent enzyme that efficiently and specifically hydrolyzes metformin to guanylurea and dimethylamine. The active enzyme is a heteromeric complex of α- and β- subunits in which only the α-subunits contain the conserved His and Asp residues for the coordination of two Ni ions in the active site. A crystal structure of metformin hydrolase reveals an αβ stoichiometry of the hexameric complex, which is unprecedented in the ureohydrolase family. By studying a closely related but more widely distributed enzyme, we find that the putative predecessor specifically hydrolyzes dimethylguanidine instead of metformin. Our findings establish the molecular basis for metformin hydrolysis to guanylurea as the primary pathway for metformin biodegradation and provide insight into the recent evolution of ureohydrolase family proteins in response to an anthropogenic compound.

PubMed: 39271653
DOI: 10.1038/s41467-024-51752-5

実験手法

X-RAY DIFFRACTION (2.06 Å)