THE COUPLING OF INTERACTION ENERGY TO CONFORMATIONAL DYNAMICS IN PEPCK CATALYSIS

PEPCK催化中相互作用能与构象动力学的耦合

• 批准号: 8170263
• 负责人: TODD HOLYOAK
• 金额: $ 0.07万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2011-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8170263
• 关键词: Catalysis; Complex; Computer Retrieval of Information on Scientific Projects Database; Coupling; Data; Enzymes; Faculty; Funding; Grant; Institution; Ligands; Modeling; Molecular Biology; Nature; Phosphoenolpyruvate Carboxylase; Process; Property; Publications; Reaction; Research; Research Design; Research Personnel; Resources; Role; Source; United States National Institutes of Health; Work; base; insight; mutant

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Our present studies involve the characterization of seven complexes of a mutant form of the enzyme PEPCK that represent all of the liganded states along the reaction coordinate. We have previously determined these same liganded states for the wild type enzyme that provided the basis for our recent PNAS publication which was also highlighted in Nature Structural and Molecular Biology and the Faculty of 1000. These studies represent a continuation of that previous work. The current structural studies are designed to support our model that states, in contrast to recent studies suggesting the importance of conformational dynamics in transition state stabilization, our current biophysical data is consistent with the role of conformational dynamics in PEPCK catalysis functioning in the stabilization of the reactive catalytic intermediate, a ground state process. In order to support our other biophysical data we need to obtain structural data on the same crystallographic complexes as were previously determined at SSRL for the wild-type enzyme. Clearly the successful completion of these studies will provide a great deal of insight into our fundamental understanding of the role of the dynamic properties of enzymes in catalytic function.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 我们目前的研究涉及表征的突变形式的酶PEPCK，代表所有的配位状态沿着反应坐标的7个复合物。 我们之前已经确定了野生型酶的这些相同的配体状态，这为我们最近的PNAS出版物提供了基础，该出版物也在《自然结构与分子生物学》和《Faculty of 1000》中得到了强调。这些研究是以前工作的继续。 目前的结构研究的目的是支持我们的模型，国家，在最近的研究表明，在过渡态稳定的构象动力学的重要性相反，我们目前的生物物理数据是一致的作用，构象动力学在PEPCK催化功能的稳定反应性催化中间体，基态过程。为了支持我们的其他生物物理数据，我们需要获得与先前在SSRL确定的野生型酶相同的晶体复合物的结构数据。 显然，这些研究的成功完成将为我们对酶的动力学性质在催化功能中的作用的基本理解提供大量的见解。