The phosphate moiety of phosphoenolpyruvate does NOT contribute to allosteric regulation of liver pyruvate kinase by fructose-1,6-bisphosphate ✝.

The phosphate moiety of phosphoenolpyruvate does NOT contribute to allosteric regulation of liver pyruvate kinase by fructose-1,6-bisphosphate✝.
Arch Biochem Biophys. 2020 Oct 16;:108633
Authors: Chappell BM, Fenton AW
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 enzyme-substrate interactions. When evaluating allosteric regulation in human liver pyruvate kinase, the use of a range of monovalent cations (K+, NH4+, Rb+, Ca+, 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-...

Source: Archives of Biochemistry and Biophysics - October 16, 2020 Category: Biochemistry Authors: Chappell BM, Fenton AW Tags: Arch Biochem Biophys Source Type: research