RAY STEVENS PRT TIME

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 用过渡态类似物免疫会产生一种种系编码的抗体，它催化己二烯重排成醛，其速度接近于由分支酸变位酶催化的相关周环反应。亲和成熟产生抗体AZ-28，它有六个氨基酸取代，其中一个会导致催化速率下降。为了了解该体系中结合与催化速率之间的关系，我们对一系列活性中心突变体进行了表征，并用过渡态类似物测定了AZ-28配合物的三维晶体结构。这一分析表明，激活能依赖于几个立体电子效应的复杂平衡，这些立体电子效应由活性中心中广泛的结合相互作用网络控制。

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. Immunization with transition state analogue results in a germline-encoded antibody that catalyses the rearrangement of hexadiene to aldehyde with a rate approaching that of a related pericyclic reaction catalysed by the enzyme chorismate mutase. Affinity maturation gives antibody AZ-28, which has six amino acid substitutions, one of which results in a decrease in catalytic rate. To understand the relationship between binding and catalytic rate in this system we characterized a series of active-site mutants and determined the 3-D crystal structure of the complex of AZ-28 with the transition state analogue. This analysis indicates that the activation energy depends on a complex balance of several stereoelectronic effects which are controlled by an extensive network of binding interactions in the active site.