Bidirectional allosteric ligand regulation in a central glycolytic enzyme.

ABSTRACT: Allosteric regulation enables fine-tuned control of enzyme activity in response to cellular signals, yet its molecular basis often remains unclear. Phosphofructokinase-1 (PFK), the rate-limiting enzyme of glycolysis, is a paradigmatic, well-conserved system whose reaction kinetics conform to the Monod-Wyman-Changeux model of allostery. However, X-ray crystal structures of bacterial PFK orthologs in distinct ligand-bound states do not show the consistent, concerted structural rearrangements expected for classical "relaxed" and "tense" states, revealing a decades-long disconnect between structure and function. We resolve this paradox by integrating biophysical and computational approaches to show that activator and inhibitor binding to the same allosteric pocket differentially reweight the c

SUBMITTER: Sundberg B 

PROVIDER: S-EPMC12889660 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature