STRUCTURE AND FUNCTION OF FORMALDEHYDE DEHYDROGENASE

甲醛脱氢酶(FDH)或谷胱甘肽依赖的甲醛脱氢酶(FDH或xx-乙醇脱氢酶)是生物体解毒甲醛的两条途径之一。它特异地氧化S-羟甲基谷胱甘肽(谷胱甘肽与甲醛形成的加合物)为S-甲酰谷胱甘肽，同时伴随NAD的还原。外佣还氧化长链伯醇。本研究旨在用结构和动力学方法研究甲醛脱氢酶的催化机理。X射线结晶学的结构研究将专门针对底物结合和催化过程中酶的结构变化进行研究。涉及同位素效应和稳态前动力学的动力学研究将旨在确定FDH的整个动力学机制，包括通过结晶学观察到的结构变化的速度。结构和动力学方法将在严格分析该酶催化过程中发生的事件方面相辅相成。了解FDH的催化机理将有助于理解对甲醛解毒有重大贡献的过程。

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.