RUI: The Sources of Substrate Specificity in Hydroquinone Dioxygenases

生命过程化学（CLP）计划中的这一奖项，与分子和细胞生物科学（MCB）部门共同资助，支持惠特曼学院的Tim Machonkin教授的工作，以了解某些酶如何结合的基本决定因素并对氯化氢醌进行化学转化。有些细菌具有分解稳定芳香化合物的非凡能力，包括在极少数情况下的氯化芳香化合物。某些类型的含铁酶参与这些过程。其中研究最少的是那些专门识别和切割氯化氢醌。这些对苯二酚双加氧酶似乎是最近进化出来的，可以降解从人类活动进入环境的合成化合物。决定这些酶如何特异性地识别和进行氯化对苯二酚的开环反应的因素是未知的。因此，对苯二酚双加氧酶提供了一个理想的平台，用于了解蛋白质如何特异性地结合氯化分子并激活它们进行化学转化，以及金属酶如何（如含铁的环裂解酶）进化出新的功能。这项工作将使相当数量的本科生沉浸在涉及一系列技术的前沿生物化学研究中，促进教学和研究在这个主要是本科院校的整合。从这项研究中获得的知识可以应用于其他类别的含铁酶，涉及芳香分子的分解，并可能导致具有新特性的酶的工程化。反过来，这可能导致改进的方法，用于生物修复的氯化芳香分子，这是常见的棘手的环境污染物。

This award in the Chemistry of Life Processes (CLP) program, co-funded with the Division of Molecular and Cellular Biosciences (MCB), supports work by Professor Tim Machonkin at Whitman College to understand the fundamental determinants of how certain enzymes bind and carry out chemical transformations on chlorinated hydroquinones. Some bacteria have the remarkable ability to break down stable aromatic compounds, including in rare cases chlorinated aromatics. Certain types of iron-containing enzymes are involved in these processes. Among the least studied are ones that specifically recognize and cleave chlorinated hydroquinones. These hydroquinone dioxygenases appear to have evolved recently to degrade synthetic compounds that entered the environment from human activity. The factors that determine how these enzymes specifically recognize and carry out the ring-cleaving reaction on chlorinated hydroquinones are unknown. Thus, hydroquinone dioxygenases provide an ideal platform for learning how proteins can specifically bind chlorinated molecules and activate them for chemical transformations, as well as how metalloenzymes (such as iron-containing ring-cleaving enzymes) evolve new functions.This work will immerse a significant number of undergraduate students in cutting-edge biochemical research involving an array of techniques, promoting the integration of teaching and research at this primarily undergraduate institution. The knowledge gained from this research could be applied to other classes of iron-containing enzymes involved the breakdown of aromatic molecules, and could lead to engineering of enzymes with novel properties. This, in turn, could lead to improved methods for bioremediation of chlorinated aromatic molecules, which are common intractable environmental pollutants.