Reference: Hwang PK and Fletterick RJ (1986) Convergent and divergent evolution of regulatory sites in eukaryotic phosphorylases. Nature 324(6092):80-4

Reference Help

Abstract

The activity of many proteins in eukaryotic cells is regulated by reversible covalent phosphorylation. This regulatory modification is often linked to other allosteric controls within the same protein, and such overlapping regulatory mechanisms are best characterized for glycogen phosphorylase (EC 2.4.1.1). Phosphorylases from different organisms or cell types exhibit markedly contrasting regulatory features; this makes the enzyme attractive for studying the evolution of interacting molecular regulatory mechanisms. Extensive biochemical and crystallographic studies of rabbit muscle phosphorylase have led to a characterization of five regulatory regions (phosphorylation, glycogen storage, AMP, glucose and purine sites). Here we report the complete primary structure of the yeast Saccharomyces cerevisiae glycogen phosphorylase, deduced from the sequence of the cloned gene. Regions that are highly conserved between muscle and yeast enzymes include the active site, the glycogen storage site and possibly the glucose and purine inhibition sites. Partial conservation of the residues involved in AMP-binding suggests a binding site for the yeast enzyme inhibitor, glucose 6-phosphate. Other parts of the AMP site and the intersubunit contacts involved in AMP allostery are disrupted in the yeast enzyme by extreme sequence divergence. The poor alignment of amino termini and lack of homology at phosphorylation sites indicate that regulation by reversible phosphorylation evolved independently in yeast and vertebrate phosphorylases.

Reference Type
Journal Article
Authors
Hwang PK, Fletterick RJ
Primary Lit For
Additional Lit For
Review For

Interaction Annotations

Increase the total number of rows showing on this page by using the pull-down located below the table, or use the page scroll at the table's top right to browse through the table's pages; use the arrows to the right of a column header to sort by that column; filter the table using the "Filter" box at the top of the table; click on the small "i" buttons located within a cell for an annotation to view further details about experiment type and any other genes involved in the interaction.

Interactor Interactor Type Assay Annotation Action Modification Phenotype Source Reference

Gene Ontology Annotations

Increase the total number of rows showing on this page using the pull-down located below the table, or use the page scroll at the table's top right to browse through the table's pages; use the arrows to the right of a column header to sort by that column; filter the table using the "Filter" box at the top of the table.

Gene Gene Ontology Term Qualifier Aspect Method Evidence Source Assigned On Annotation Extension Reference

Phenotype Annotations

Increase the total number of rows showing on this page using the pull-down located below the table, or use the page scroll at the table's top right to browse through the table's pages; use the arrows to the right of a column header to sort by that column; filter the table using the "Filter" box at the top of the table; click on the small "i" buttons located within a cell for an annotation to view further details.

Gene Phenotype Experiment Type Mutant Information Strain Background Chemical Details Reference

Regulation Annotations

Increase the total number of rows displayed on this page using the pull-down located below the table, or use the page scroll at the table's top right to browse through the table's pages; use the arrows to the right of a column header to sort by that column; to filter the table by a specific experiment type, type a keyword into the Filter box (for example, “microarray”); download this table as a .txt file using the Download button or click Analyze to further view and analyze the list of target genes using GO Term Finder, GO Slim Mapper, SPELL, or YeastMine.

Regulator Target Experiment Assay Construct Conditions Strain Background Reference