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首页> 外文期刊>Biochemistry >Model of a quinary structure between Krebs TCA cycle enzymes: a model for the metabolon
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Model of a quinary structure between Krebs TCA cycle enzymes: a model for the metabolon

机译：Krebs TCA循环酶之间的五元结构模型：代谢产物模型

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The enzymes which are responsible for catalyzing sequential reactions in several metabolic pathways have been proposed to be highly organized in supramolecular complexes termed metabolons. However, the in situ existence of these weak complexes is difficult to demonstrate because many of them are dissociated during isolation due to dilution effects. Consequently, the metabolon concept is subject to controversy. A model system consisting of genetically prepared bienzymatic fusion proteins has been used to immobilize sequential metabolic enzymes in close proximity and to demonstrate possible kinetic advantages of metabolons. These experiments use the sequential Krebs TCA cycle enzymes from yeast mitochondrial malate dehydrogenase (MDH), citrate synthase (CS), and aconitase (ACO). Using the porcine high-definition structures of these three enzymes, we have performed computer-modeling studies in order to understand how the molecules may interact. Among the thousands of docking orientations we have tried, one was found to respond to the structural and experimental constraints from the results obtained with the yeast fusion proteins. Interestingly, this quinary structure model shows substantial interacting surface areas with spatial and electrostatic complementarities which make the complex thermodynamically stable. This structure also contains an unbroken electrostatically favorable channel connecting the active sites of ACO and CS, as well as the one previously reported between CS and MDH active sites. Charged amino acids which could be involved in interactions stabilizing the complex have been identified. This model will be used as the basis for further experimental work on the structure of the Krebs TCA cycle metabolon.
机译：已经提出负责催化几种代谢途径中的顺序反应的酶在被称为代谢子的超分子复合物中是高度组织的。但是，这些弱复合物的原位存在难以证明，因为由于稀释作用，它们中的许多在分离过程中都离解了。因此，新陈代谢的概念受到争议。由遗传制备的双酶融合蛋白组成的模型系统已用于固定顺序代谢酶的位置，并证明了代谢子的可能动力学优势。这些实验使用来自酵母线粒体苹果酸脱氢酶（MDH），柠檬酸合酶（CS）和乌头酸酶（ACO）的顺序Krebs TCA循环酶。使用这三种酶的猪高清结构，我们进行了计算机建模研究，以了解分子之间可能如何相互作用。在我们尝试的数千种对接方向中，发现一种响应于酵母融合蛋白获得的结构和实验限制。有趣的是，这种五元结构模型显示出具有空间和静电互补性的大量相互作用表面积，这使复杂的热力学稳定。该结构还包含一个连接ACO和CS活性位点的不间断的静电有利通道，以及先前报道的CS和MDH活性位点之间的通道。已鉴定出可能参与稳定复合物相互作用的带电荷氨基酸。该模型将用作进一步研究Krebs TCA循环代谢子结构的基础。

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