Year: 2025
Type: article
Abstract: Prostaglandin Endoperoxide H Synthases (PGHS-1 and PGHS-2), also referred to as cyclooxygenases (COX-1 and COX-2), are homodimeric enzymes that oxygenate arachidonic acid (AA) to generate Prostaglandin H 2 (PGH 2 ), the precursor to prostaglandins, prostacyclin, and thromboxane. The homodimeric enzymes behave as conformational heterodimers comprised of allosteric (E allo ) and catalytic (E cat ) subunits. During catalysis, only the E cat subunit actively oxygenates AA to PGH 2 . Different ligands bind to E allo to allosterically modulate the oxygenation of AA in E cat . Biochemical studies and functional characterizations have provided compelling evidence for asymmetry between subunits of the homodimer centered at the dimer interface. However, the structural transitions responsible for mediating intersubunit communication remain elusive. This review summarizes the pivotal experiments that have shaped our current understanding of the mechanisms underlying the allosteric modulation of PGHS-1 and PGHS-2. An ensemble-based structural model, derived from one dimensional fluorine nuclear magnetic resonance spectroscopy, is presented to provide a framework of the conformational landscapes associated with the regulation of PGHS function.
Source: Journal of Biological Chemistry
Authors: Liang Dong, Michael G. Malkowski
Institution: University at Buffalo, State University of New York
Language: English
Subfield: Pharmacology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,430
OpenAlex ID: W4416145476