STRUCTURE AND FUNCTION OF FORMALDEHYDE DEHYDROGENASE

甲醛脱氢酶（FDH）或谷胱甘肽依赖性甲醛脱氢酶（FDH或xx-醇脱氢酶）构成生物体对甲醛解毒的两种途径之一。它特异性地将s-羟甲基-谷胱甘肽（谷胱甘肽和甲醛之间形成的加合物）氧化为s-甲酰基谷胱甘肽，同时还原NAD+。FDH还氧化长链伯醇。本论文旨在从结构和动力学两方面研究甲醛脱氢酶的催化机理。涉及X射线晶体学的结构研究将专门针对研究底物结合和催化过程中酶的结构变化。涉及同位素效应和稳态前动力学的动力学研究旨在确定FDH的整个动力学机制，包括通过晶体学观察到的结构变化速率。结构和动力学方法将相互补充，严格分析该酶催化过程中发生的事件。了解FDH的催化机理将有助于理解对甲醛解毒有重要贡献的过程。

Formaldehyde dehydrogenase (FDH) or glutathione-dependent formaldehyde dehydrogenase (FDH or xx-alcohol dehydrogenase) constitutes one of the two pathways by which living organisms detoxify formaldehyde. It specifically oxidizes s-hydroxymethyl-glutathione (an adduct formed between glutathione and formaldehyde) to s- formylglutathione with concomitant reduction of NAD+. FDH also oxidizes long-chain primary alcohols. This proposal aims at studying the catalytic mechanism of formaldehyde dehydrogenase by structural and kinetic methods. Structural studies involving X-ray crystallography will specifically aim at studying the structural changes in the enzyme during substrate binding and catalysis. Kinetic studies involving isotope effects and presteady state kinetics would aim at determining the entire kinetic mechanism of FDH including the rate of structural changes observe by crystallography. The structural and kinetic approach will complement each other in rigorously analyzing the events occurring during catalysis by this enzyme. Knowledge of the catalytic mechanism of FDH will lead to an understanding of the process that contributes significantly to the detoxification of formaldehyde.