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Evolution of allosteric control in glycogen phosphorylase
J W Hudson1, G B Golding, M M Crerar
1Department of Biology, York University, Ontario, Canada.
Journal of Molecular Biology
|December 5, 1993
Summary
Comparative analysis of glycogen phosphorylase enzymes reveals conserved active sites across species. Evolution suggests glucose-6-phosphate inhibition predates AMP/phosphorylation control mechanisms.
Area of Science:
- Biochemistry
- Evolutionary Biology
- Enzymology
Background:
- Glycogen phosphorylase is a key enzyme in glycogen metabolism.
- Comparative analysis of protein sequences and structures provides insights into evolutionary relationships and functional conservation.
Purpose of the Study:
- To perform a comparative sequence analysis of glycogen phosphorylases from various organisms.
- To understand the evolutionary history and functional conservation of key residues, including active site and allosteric binding sites.
Main Methods:
- Comparative sequence analysis of phosphorylases from rabbit, human, rat, Dictyostelium, yeast, potato, and Escherichia coli.
- Phylogenetic analysis to determine evolutionary relationships.
- Identification and analysis of conserved residues in active sites, allosteric sites, and dimer interfaces.
Main Results:
- A large conserved region was identified across all analyzed phosphorylases.
- Active site and pyridoxal phosphate binding residues are highly conserved; sugar binding residues are mostly conserved.
- Non-mammalian phosphorylases show poor conservation of phosphorylation and AMP binding sites but conserved glucose-6-phosphate binding sites.
- Dimer contact residues form three networks, with one linked to AMP/phosphorylation and another to glucose-6-phosphate binding.
Conclusions:
- Glucose-6-phosphate inhibition is proposed as an early allosteric control mechanism in phosphorylase evolution.
- Distinct ligand binding sites for AMP/phosphorylation control evolved later, facilitating separate dimer contact networks for activation.