RAY STEVENS PRT TIME

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。 用过渡态类似物免疫导致种系编码的抗体，该抗体催化己二烯重排为醛，其速率接近由分支酸酯酶催化的相关周环反应的速率。亲和力成熟得到抗体AZ-28，其具有六个氨基酸取代，其中一个导致催化速率降低。为了了解在这个系统中的结合和催化速率之间的关系，我们表征了一系列活性位点突变体，并确定了AZ-28与过渡态类似物的复合物的3-D晶体结构。这一分析表明，活化能取决于一个复杂的平衡的几个立体电子效应，这是由一个广泛的网络中的活性位点的结合相互作用控制。

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.