The mechanism of allosteric regulation of calcium-independent phospholipase A₂ by ATP and calmodulin binding to the ankyrin domain.

ABSTRACT: Group VIA calcium-independent phospholipase A₂ (iPLA₂) is a member of the PLA₂ superfamily that exhibits calcium-independent activity in contrast to the other two major types, secreted phospholipase A₂ (sPLA₂) and cytosolic phospholipase A₂ (cPLA₂), which both require calcium for their enzymatic activity. Adenosine triphosphate (ATP) has been reported to allosterically activate iPLA₂, and this has now been verified with a lipidomics-based mixed-micelle assay, but its mechanism of action has been unknown. Hydrogen/deuterium exchange mass spectrometry (HDX-MS) was employed to identify ATP interaction peptide regions located within the ankyrin repeat domain at which ATP interacts. Molecular dynamics simula

SUBMITTER: Mouchlis VD 

PROVIDER: S-EPMC11621833 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature