What is allosteric regulation? Exploring the exceptions that prove the rule!

Autor:	McCullagh M; Department of Chemistry, Oklahoma State University, Stillwater, Oklahoma, USA., Zeczycki TN; Department of Biochemistry and Molecular Biology, Brody School of Medicine at East Carolina University, Greenville, North Carolina, USA., Kariyawasam CS; Department of Chemistry, Mississippi State University, Mississippi State, Mississippi, USA., Durie CL; Department of Biochemistry, University of Missouri, Columbia, Missouri, USA., Halkidis K; Department of Hematologic Malignancies and Cellular Therapeutics, The University of Kansas Medical Center, Kansas City, Kansas, USA; Department of Biochemistry and Molecular Biology, The University of Kansas Medical Center, Kansas City, Kansas, USA., Fitzkee NC; Department of Chemistry, Mississippi State University, Mississippi State, Mississippi, USA., Holt JM; Department of Biochemistry and Molecular Biology, The University of Kansas Medical Center, Kansas City, Kansas, USA., Fenton AW; Department of Biochemistry and Molecular Biology, The University of Kansas Medical Center, Kansas City, Kansas, USA. Electronic address: afenton@kumc.edu.
Jazyk:	angličtina
Zdroj:	The Journal of biological chemistry [J Biol Chem] 2024 Mar; Vol. 300 (3), pp. 105672. Date of Electronic Publication: 2024 Jan 23.
DOI:	10.1016/j.jbc.2024.105672
Abstrakt:	"Allosteric" was first introduced to mean the other site (i.e., a site distinct from the active or orthosteric site), an adjective for "regulation" to imply a regulatory outcome resulting from ligand binding at another site. That original idea outlines a system with two ligand-binding events at two distinct locations on a macromolecule (originally a protein system), which defines a four-state energy cycle. An allosteric energy cycle provides a quantifiable allosteric coupling constant and focuses our attention on the unique properties of the four equilibrated protein complexes that constitute the energy cycle. Because many observed phenomena have been referenced as "allosteric regulation" in the literature, the goal of this work is to use literature examples to explore which systems are and are not consistent with the two-ligand thermodynamic energy cycle-based definition of allosteric regulation. We emphasize the need for consistent language so comparisons can be made among the ever-increasing number of allosteric systems. Building on the mutually exclusive natures of an energy cycle definition of allosteric regulation versus classic two-state models, we conclude our discussion by outlining how the often-proposed Rube-Goldberg-like mechanisms are likely inconsistent with an energy cycle definition of allosteric regulation. Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article. (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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