These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Distinct phosphorylation signals converge at the catalytic center in glycogen phosphorylases.
    Author: Lin K, Hwang PK, Fletterick RJ.
    Journal: Structure; 1997 Nov 15; 5(11):1511-23. PubMed ID: 9384566.
    Abstract:
    BACKGROUND: Glycogen phosphorylases (GPs) catalyze the conversion of the storage form of carbohydrate (glycogen) to the readily usable form (glucose-1-phosphate) to provide cellular energy. Members of this enzyme family have evolved diverse regulatory mechanisms that control a conserved catalytic function. The mammalian and yeast GPs are expressed as inactive forms requiring phosphorylation for activation. Phosphorylation of yeast GP occurs at a distinct site from that of mammalian GP. This work addresses the structural basis by which distinct activation signals relay to the conserved catalytic site in yeast and mammalian GPs. Such knowledge may help understand the principles by which diverse biological regulation evolves. RESULTS: We have compared the crystal structures of the unphosphorylated and phosphorylated forms of yeast GP and propose a relay which links phosphorylation to enzyme activation. Structural components along the activation relay becomes more conserved within the GP family downstream along the relay, towards the catalytic center. Despite distinct upstream activation signals, a response element downstream of the relay leading to the catalytic center is conserved in all GPs. The response element consists of ten hydrophobic residues dispersed over two subunits of the homodimer. Phosphorylation induces hydrophobic condensation of these residues via structural rearrangement, which triggers conformation change of the active site GATE loop, leading to enzyme activation. CONCLUSIONS: Members of the GP family with diverse activation mechanisms have evolved from a constitutively active ancestral enzyme which has the TOWER hydrophobic response element in the active position. Diverse regulation evolved as a result of evolutionary constraint on the downstream response element in the active state, coupled with flexibility and variability in elements of the upstream relays.
    [Abstract] [Full Text] [Related] [New Search]