Structural Basis of Lysosomal Phospholipase A₂ Inhibition by Zn².

ABSTRACT: Lysosomal phospholipase A₂ (LPLA₂/PLA2G15) is a key enzyme involved in lipid homeostasis and is characterized by both phospholipase A2 and transacylase activity and by an acidic pH optimum. Divalent cations such as Ca²⁺ and Mg²⁺ have previously been shown to have little effect on the activity of LPLA₂, but the discovery of a novel crystal form of LPLA₂ with Zn²⁺ bound in the active site suggested a role for this divalent cation in regulating enzyme activity. In this complex, the cation directly coordinates the serine and histidine of the α/β-hydrolase triad and stabilizes a closed conformation. This closed conformation is characterized by an inward shift of the lid loop, which extends over the active site and effe

SUBMITTER: Bouley RA 

PROVIDER: S-EPMC6677152 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature