Studies on the Mechanism and Control of Enzyme Action

建议进行涉及核磁共振波谱的研究，这些研究将使我们能够测量配体结合的动力学，并且还将提供对底物和效应物之间存在的空间关系的理解，当它们与酶结合时。将用pH动力学方法研究酶上与催化和底物结合有关的酸性和碱性基团。CyS344的修饰会导致酶失活。这种影响是由于CyS344位于活性位点，还是修饰只是阻止了AMPS合成酶的天然构象，将使用定点突变的方法进行研究。腺苷琥珀酸(AMPS)合成酶是从IMP生物合成AMP的第一步，因此在代谢中起着关键作用。这种酶如何作为催化剂，以及它如何在分子水平上受到调控，对于理解它在新陈代谢中的基础作用至关重要。

Studies are proposed involving nuclear magnetic resonance spectroscopy that will permit us to measure the kinetics of ligand binding and that will also provide an understanding of the spatial relationships that exist among substrates and effectors when they are bound to the enzyme. Acidic and basic groups on the enzyme associated with catalysis and substrate binding will be studied using the protocol of pH kinetics. Modification of CyS344 leads to enzyme inactivation. Whether this effect is due to CyS344 being at the active site, or whether modification simply prevents AMPS synthetase from assuming its native conformation, will be investigated using the protocol of site-specific mutagenesis. Adenylosuccinate (AMPS) synthetase if the first committed step in AMP biosynthesis from IMP and therefore plays a pivotal role in metabolism. How this enzyme acts as a catalyst and how it is regulated at the molecular level is crucial to an understanding of its fundamental role in metabolism.