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: The phosphate moiety of phosphoenolpyruvate does NOT contribute to allosteric regulation of liver pyruvate kinase by fructose-1,6-bisphosphate✝.
    Author: Chappell BM, Fenton AW.
    Journal: Arch Biochem Biophys; 2020 Nov 30; 695():108633. PubMed ID: 33075302.
    Abstract:
    A linked-function theory for allostery allows for a differentiation between those protein-ligand interactions that contribute the most to ligand binding and those protein-ligand interactions that contribute to the allosteric mechanism. This potential distinction is the basis for analogue studies used to determine which chemical moieties on the allosteric effector contribute to allostery. Although less recognized, the same separation of functions is possible for substrate-enzyme interactions. When evaluating allosteric regulation in human liver pyruvate kinase, the use of a range of monovalent cations (K+, NH4+, Rb+, Cs+, cyclohexylammonium+ and Tris+) altered substrate (phosphoenolpyruvate; PEP) affinity, but maintained similar allosteric responses to the allosteric activator, fructose-1,6-bisphosphate (Fru-1,6-BP). Because crystal structures indicate that the active site monovalent cation interacts directly with the phosphate moiety of the bound PEP substrate, we questioned if the phosphate moiety might contribute to substrate binding, but not to the allosteric mechanism. Here, we demonstrate that the binding of oxalate, a non-phosphorylated substrate/product analogue, is allosterically enhanced by Fru-1,6-BP. That observation is consistent with the concept that the phosphate moiety of PEP is not required for the allosteric function, even though that moiety likely contributes to determining substrate affinity.
    [Abstract] [Full Text] [Related] [New Search]