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PMID: 2557623 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Evolution of a bifunctional enzyme: 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 86 ·No. 24 ·1989-12-00 ·Pages 9642-6

Bazan JF, Fletterick RJ, Pilkis SJ

Abstract

The bifunctional rat liver enzyme 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (ATP:D-fructose-6-phosphate 2-phosphotransferase/D-fructose-2,6-bisphosphate 2-phosphohydrolase, EC 2.7.1.105/EC 3.1.3.46) is constructed of two independent catalytic domains. We present evidence that the kinase and bisphosphatase halves of the bifunctional enzyme are, respectively, structurally similar to the glycolytic enzymes 6-phosphofructo-1-kinase and phosphoglycerate mutase. Computer-assisted modeling of the C-terminal bisphosphatase domain reveals a hydrophobic core and active site residue constellation equivalent to the yeast mutase structure; structural differences map to length-variable, surface-located loops. Sequence patterns derived from the structural alignment of mutases and the bisphosphatase further detect a significant similarity to a family of acid phosphatases. The N-terminal kinase domain, in turn, is predicted to form a nucleotide-binding fold that is analogous to a segment of 6-phosphofructo-1-kinase, suggesting that these unrelated enzymes bind fructose 6-phosphate and ATP substrates in a similar geometry. This analysis indicates that the bifunctional enzyme is the likely product of gene fusion of kinase and mutase/phosphatase catalytic units.

MeSH Terms
Acid Phosphatase/genetics Amino Acid Sequence Animals Biological Evolution Bisphosphoglycerate Mutase/genetics Humans Models, Structural Molecular Sequence Data Phosphofructokinase-2 Phosphoric Monoester Hydrolases/genetics Phosphotransferases/genetics Protein Conformation Sequence Homology, Nucleic Acid Software
Chemicals
Phosphotransferases Phosphofructokinase-2 Acid Phosphatase Phosphoric Monoester Hydrolases Bisphosphoglycerate Mutase
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Bazan J F
Department of Biochemistry and Biophysics, University of California, San Francisco 94143.
Fletterick R J
Pilkis S J
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43 references, click to expand
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.86.24.9642
Published
1989-12-00
Pages
9642-6
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC298557
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.86.24.9642 PMC Full Text View journal details
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