8X3G

Crystal structure of metformin hydrolase from Aminobacter

8X3G の概要

• エントリーDOI: 10.2210/pdb8x3g/pdb
• 分子名称: Agmatinase family protein, Arginase family protein, GLYCEROL, ... (5 entities in total)
• 機能のキーワード: metformin hydrolase, arginase family, heterohexamer, hydrolase
• 由来する生物種: Aminobacter sp. NyZ550; 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 236950.54

構造登録者

Li, T.,Zhou, N.Y. (登録日: 2023-11-13, 公開日: 2024-09-11)

主引用文献

Li, T.,Xu, Z.J.,Zhang, S.T.,Xu, J.,Pan, P.,Zhou, N.Y.
Discovery of a Ni 2+ -dependent heterohexameric metformin hydrolase.
Nat Commun, 15:6121-6121, 2024

PubMed Abstract: The biguanide drug metformin is a first-line blood glucose-lowering medication for type 2 diabetes, leading to its presence in the global environment. However, little is known about the fate of metformin by microbial catabolism. Here, we characterize a Ni-dependent heterohexameric enzyme (MetCaCb) from the ureohydrolase superfamily, catalyzing the hydrolysis of metformin into guanylurea and dimethylamine. Either subunit alone is catalytically inactive, but together they work as an active enzyme highly specific for metformin. The crystal structure of the MetCaCb complex shows the coordination of the binuclear metal cluster only in MetCa, with MetCb as a protein binder of its active cognate. An in-silico search and functional assay discover a group of MetCaCb-like protein pairs exhibiting metformin hydrolase activity in the environment. Our findings not only establish the genetic and biochemical foundation for metformin catabolism but also provide additional insights into the adaption of the ancient enzymes toward newly occurred substrate.

PubMed: 39033196
DOI: 10.1038/s41467-024-50409-7

実験手法

X-RAY DIFFRACTION (1.84 Å)