EVOLUTION OF PHOSPHOFRUCTOKINASE - GENE DUPLICATION AND CREATION OF NEW EFFECTOR SITES
EVOLUTION OF PHOSPHOFRUCTOKINASE - GENE DUPLICATION AND CREATION OF NEW EFFECTOR SITES
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DOI：
10.1038/309467a0
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发表时间：
1984-01-01
期刊：
影响因子：
64.8
通讯作者：
HEINRIKSON, RL
中科院分区：
文献类型：
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作者：
POORMAN, RA;RANDOLPH, A;HEINRIKSON, RL
磷酸果糖激酶（PFK; EC 2.7.1.11）是在糖酵解调节中具有关键作用的四聚体酶1;因此，它们受到各种代谢物的变构活化和抑制2。真核生物PFK的大小约为原核生物酶的两倍，并且受更广泛的效应物库调节：例如，兔肌肉（RM）PFK和嗜热脂肪芽孢杆菌（Bs）PFK的亚基分子量分别为82，000和36，000。这两种酶都被ADP（或AMP）激活，但RM-PFK也被果糖二磷酸（FBP）激活，并被ATP和柠檬酸盐抑制。这与其他证据一起导致了哺乳动物PFK通过原核基因的复制进化的推测3 -5，尽管先前的肽分析6未能揭示RM-PFK的内部同源性。在这里，我们证明了清楚的同源性之间的N-和C-一半的RM-PFK和Bs-PFK，从而建立了一个进化关系的系列基因重复和分歧。此外，Bs-PFK结构的详细知识提供了关于RM-PFK的结构组织和酶四聚体中新效应位点的进化的推断的基础。
Phosphofructokinases (PFK; EC 2.7.1.11) are tetrameric enzymes that have a key role in the regulation of glycolysls1; as such, they are subject to allosteric activation and inhibition by various metabolites2. Eukaryotic PFKs are about twice the size of prokaryotic enzymes and are regulated by a wider repertoire of effectors: for example, the subunit molecular weights of rabbit muscle (RM) PFK andBacillus stearothermophilus(Bs) PFK are 82,000 and 36,000, respectively. Both enzymes are activated by ADP (or AMP), but RM-PFK is also activated by fructose bisphosphates (FBP) and inhibited by ATP and citrate. This, together with other evidence, has led to speculation that mammalian PFKs have evolved by duplication of a prokaryotic gene3–5, although previous peptide analysis6failed to reveal internal homology in RM-PFK. Here we demonstrate clear homology among the N- and C-halves of RM-PFK and Bs-PFK, thus establishing an evolutionary relationship by series gene duplication and divergence. Furthermore, detailed knowledge of the Bs-PFK structure provides the basis for inferences concerning the structural organization of RM-PFK and the evolution of new effector sites in the enzyme tetramer.