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Evolution of phosphofructokinase—gene duplication and creation of new effector sites

Nature volume 309, pages 467–469 (1984)Cite this article

Abstract

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 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 gene3–5, although previous peptide analysis6 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.

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Author notes

  1. Anne Randolph

    Present address: Chiron Corp., Emeryville, California, 94608, USA

Authors and Affiliations

  1. Department of Biochemistry, The University of Chicago, 920 E. 58th Street, Chicago, Illinois, 60637, USA

    Roger A. Poorman & Robert L. Heinrikson

  2. Department of Biological Chemistry and Structure, The Chicago Medical School, North Chicago, Illinois, 60064, USA

    Anne Randolph & Robert G. Kemp

Authors
  1. Roger A. Poorman
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  2. Anne Randolph
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  3. Robert G. Kemp
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  4. Robert L. Heinrikson
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Poorman, R., Randolph, A., Kemp, R. et al. Evolution of phosphofructokinase—gene duplication and creation of new effector sites. Nature 309, 467–469 (1984). https://doi.org/10.1038/309467a0

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