麻豆淫院

A collaborative research team has successfully developed designer enzymes that exhibit both intrinsic and extrinsic functions by transplanting a synthetic trinuclear zinc center into a human cytokine.

The study is in the journal Nature Communications. The research team was led by Associate Professor Yasunori Okamoto from the Exploratory Research Center on Life and Living Systems (ExCELLS) and the Institute for Molecular Science (IMS).

The researchers targeted the human macrophage migration inhibitory factor (MIF), a cytokine with a trimeric structure containing a central cavity ideal for synthetic trinuclear zinc center installation. To precisely arrange multiple metal ions within the protein, the research team combined geometric search algorithms and quantum chemical calculations.

Using systematic computational geometric searches, the team identified optimal amino acid arrangements capable of stably maintaining trinuclear zinc centers. Density functional theory (DFT) calculations further narrowed down potential candidates.

X鈥憆ay crystallographic analysis successfully confirmed the formation of trinuclear zinc structures as designed. The resulting designer enzyme demonstrated top鈥憈ier hydrolytic activity among the designer metalloenzymes reported to date. Remarkably, the designer enzyme retained MIF's original tautomerase activity, achieving dual functionality.

This research offers insights into designing metalloenzymes possessing a multinuclear metal center, which are typically found in natural metalloenzymes catalyzing highly challenging chemical transformations, potentially leading to green chemical transformation technologies.

Additionally, since cytokines are signal transducing molecules involved in various biological phenomena, this cytokine鈥慴ased designer enzyme holds promise as a life phenomenon鈥憆esponsive chemical tool.