ORGANIZATION AND REGULATION OF THE ATCASE CISTRONS

这项研究的目的是为了更好地理解 代谢途径中涉及的集成调控逻辑需要 始终如一，但对环境友好的活动。最多的两个 新陈代谢调节的常见基本模式包括控制 基因表达与酶活性的生化调控 它们已经在细胞中产生了。的经典交互 这两个系统正在接受审查，由 大肠杆菌中嘧啶和精氨酸代谢的相互关系 Coli.控制这些必需生物合成的关键酶 途径是天冬氨酸氨基转移酶(ATCase)，它具有一种 氨基甲酰磷酸进入新生代谢流的作用 精氨酸或嘧啶核苷酸的生物合成。而E. Coli系统提供了最复杂的集成控制模型， 另一种重要的监管模式是以进化模式发展起来的 其中各个酶的步骤被同化成一个 紧凑的建筑单元中的多功能生化步骤。 在集中精力进行结构组织和监管的同时， 在大肠杆菌中的PYRLBIX操纵子，本研究程序对比了该系统 与不同的结构组织和相关的监管变化 在高等生物(酵母、粘阿米巴、植物和仓鼠)中观察到 以加深对变构调节的理解 天冬氨酸氨基转移酶自广泛的化学，突变和 结晶学数据是可用的。此外，还有可能形成 通过交换离散的遗传盒来激活杂交基因系统 在功能和结构上不同的酶系统涉及或 与大肠杆菌酶有关。这些研究表明， 是保守的遗传模块，可以按模式重新排列 与AA“通过盒式磁带洗牌实现模块进化”一致。确实有 影响基因表达的四种重叠遗传机制 PYRLBIX操纵子(衰减、翻译阻断、天然启动子 以及对内源核苷酸池的RNA聚合酶反应。在……里面 此外，吡喃X顺反子编码一种蛋白质，这种蛋白质是 用调节多肽和催化多肽的顺反子表达 ATCase的。这种蛋白质的用途尚不清楚，但它已经 纯化后与某些单抗具有免疫学交叉同一性 抗ATCase催化链的抗体。机械性的细节 这一系统的生理意义将被检验 这些控制将被整合到对 代谢流过的关键调节酶的嘧啶和 精氨酸生物合成。

This research is oriented toward understanding the development of the integrated regulatory logic involved in metabolic pathways that require consistent, yet environmentally-responsive, activity. The two most common, basic patterns of metabolic regulation involve the control of gene expression and the biochemical modulation of the activity of enzymes which have already been produced in the cell. The classic interaction of these two systems is being examined in the control of the interrelationship of pyrimidine and arginine metabolism in Escherichia coli. The pivotal enzyme in the control of these essential biosynthetic pathways is aspartate transcarbamoylase (ATCase) and it has a modulating role in the metabolic flux of carbamoyl phosphate into the de novo biosynthesis of either arginine or pyrimidine nucleotides. While the E. coli system provides the most sophisticated model of integrated controls, another pattern of regulatory importance develops in an evolutionary mode in which the individual enzymatic steps become assimilated into a multifunctional biochemical steps within a compact architectural unit. While concentrating on the structural organization and regulation of the pyrLBIX operon in E. coli, this research program contrasts this system with the divergent structural organization and related regulatory changes observed in higher organisms (yeast, myxamoeba, plants and hamster) in order to further an understanding of the allosteric regulation of aspartate transcarbamoylase since extensive chemical, mutational and crystallographic data are available. Furthermore, it is possible to form active hybrid gene systems by exchanging discrete genetic cassettes from functionally and structurally divergent enzymes systems involving or related to the E coli enzyme. These studies have indicated that there are conserved genetic modules which can be rearranged in patterns consistent with aa "modular evolution by cassette shuffling". There are four overlapping genetic mechanisms which affect the expression of the pyrLBIX operon (attenuation, translational blocking, native promoter access, and RNA polymerase response to endogenous nucleotide pools. In addition, the pyrX cistron encodes a protein which is coordinately expressed with the cistrons for the regulatory and catalytic polypeptides of ATCase. The purpose of this protein is unknown but it has been purified and has immunological cross-identity with some monoclonal antibodies against the ATCase catalytic chain. The mechanistic details of this system will be examined and the physiological significance of these controls will be integrated into a detailed understanding of the metabolic flux through the key regulating enzymes for pyrimidine and arginine biosynthesis.