TAGATOSE-1,6-BIPHOSPHATE ALDOLASE

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。 本项目研究了化脓性链球菌产塔格糖-1，6-二磷酸(TBP)醛缩酶的结构与功能之间的关系。除底物TBP外，TBP醛缩酶还能裂解其他三种双磷酸化D-己糖：1，6-二磷酸果糖、1，6-二磷酸山梨糖和1，6-二磷酸果糖。这四种糖都是非对映异构体，只有在碳3和碳4的立体化学上不同之处在于它们的羟基构型。正是对这一有趣的非特异性切割机制的阐明，促使我们对化脓性链球菌的TBP醛缩酶进行了结构和酶学研究。各种酶中间体的一些结构已经被解决，并正在根据详细的动力学研究进行分析。第二个目标是检查这种酶的高度同源同源物的作用，它直接结合化脓性链球菌毒力基因表达的调节因子。TBP醛缩酶同源基因被认为能够通过与调节子的结合将环境线索传递给基因表达调控机制。假设之一是，酶与其天然底物二羟基丙酮-P结合会导致酶结构的构象变化，从而使调节剂得以隔离。检验直音功能这一假说的结构研究正在进行中。

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. This project investigates a fascinating structure-function relationship in tagatose-1,6-biphosphate (TBP) aldolase from Streptococcus pyogenes. TBP aldolase can cleave, apart from its own substrate TBP, three other bisphosphorylated D-hexoses: fructose-1,6-bisphosphate, sorbose-1,6-bisphosphate and psicose-1,6-bisphosphate. These four sugars are diastereoisomers and differ only in stereochemistry at carbon 3 and at carbon 4 with respect to the configuration of their hydroxyl groups. It is the elucidation of this intriguing nonspecific cleavage mechanism that prompted our structural and enzymatic study of the TBP aldolase from S. pyogenes. A number of structures of various enzymatic intermediates have been solved and are being analyzed in the light of detailed kinetic studies.A second objective is to examine the role of a highly homologous orthologue of this enzyme that binds directly a regulator of virulence genes expression in S. pyogenes. The TBP aldolase orthologue is thought to be able to convey environmental cues to the gene expression regulation machinery via its binding to the regulator. The hypothesis is one of binding by the enzyme with its natural substrate dihydroxyacetone-P induces conformational changes in the enzyme's structure that allow sequestration of the regulator. Structural studies to examine this hypothesis of orthologue function are under way.