Poorman R A, Randolph A, Kemp R G, Heinrikson R L
Nature. 1984;309(5967):467-9. doi: 10.1038/309467a0.
Phosphofructokinases (PFK; EC 2.7.1.11) are tetrameric enzymes that have a key role in the regulation of glycolysis; as such, they are subject to allosteric activation and inhibition by various metabolites. 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 and Bacillus 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 gene, although previous peptide analysis failed 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.
磷酸果糖激酶（PFK；EC 2.7.1.11）是四聚体酶，在糖酵解调节中起关键作用；因此，它们受到各种代谢物的变构激活和抑制。真核生物的PFK大小约为原核生物酶的两倍，并且受更广泛的效应物调节：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。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和柠檬酸抑制。这一点以及其他证据引发了一种推测，即哺乳动物的PFK是通过原核基因的复制进化而来的，尽管之前的肽分析未能揭示RM-PFK内部的同源性。在这里，我们证明了RM-PFK和Bs-PFK的N端和C端之间存在明显的同源性，从而通过串联基因复制和分化建立了进化关系。此外，对Bs-PFK结构的详细了解为推断RM-PFK的结构组织以及该酶四聚体中新效应位点的进化提供了基础。
