Structure Function Correlation of G-Proteins

本研究的目的是探索G蛋白作用的一般分子基础。这将包括：a)继续研究催化Gln61在RasGAP系统中的作用，并将其扩展到其他相关系统，如Gas、Gia1和RanGAP，在这些系统中，相关的谷氨酰胺残基起主要的催化作用。B)对不同G蛋白的作用进行比较研究，重点是转导蛋白、EF-Tu、GAS和Gia1。C)建立G蛋白和TS类似物(TSA)的络合物结构与实际过渡态(TSS)结构之间的关系。D)对F1-ATPase的作用机理和能量学进行研究。E)研究蛋白质相互作用对RAS/Raf系统信号转导的影响。G蛋白及其附属蛋白的结构信息的可用性为更全面地了解控制信号转导的因素提供了独特的机会。这需要定量的结构函数关联，它可以将可用的结构信息转换为活化能，从而转换为相关的速率常数和催化效应。本项目的目标是进一步发展这种相关性，并探索信号转导G蛋白和能量转导蛋白如F1-ATPase的一般机制。这些研究有望促进对生物学中磷酸基转移本质的理解以及对信号转导的分子细节的理解。

The objective of this research is to explore the general molecular basis for the action of G-proteins. This will include: a) continuing studies of the role of the catalytic Gln61 in the RasGAP system and extending it to other related systems such as Gas, Gia1, and RanGAP, where related glutamine residues play a major catalytic role. b) Conducting a comparative study of the action of different G-proteins, focusing on transducin, EF-Tu, Gas and Gia1. c) Establishing the relationship between the structures of complexes of G-proteins and TS analogues (TSAs) and the structure of actual transition states (TSs). d) Conducting studies of the mechanism and energetics of F1-ATPase. e) Examining the effect of protein-protein interaction on signal transduction in the Ras/Raf system.The availability of structural information about G proteins and their accessory proteins offers a unique opportunity for a more complete understanding of the factors that control signal transduction. This requires a quantitative structure function correlation that can convert the available structural information to activation energies and therefore to the relevant rate constants and catalytic effects. The objective of this project is to further develop such correlations and explore the general mechanism of signal transducing G proteins and energy transducing proteins like F1-ATPase. These studies are expected to advance the understanding of the nature of phosphoryl transfer in biology as well as the understanding of the molecular details of signal transduction.