Structural and Energetic Evidence Supports the Non-Covalent Phosphate Cyclization by the Class II Phospholipase D from <i>Loxosceles intermedia</i>.

ABSTRACT: Phospholipase D (PLD) enzymes from Loxosceles spider venom mediate envenomation pathology by cleaving phospholipid headgroups. We revisited the crystal structure of Loxosceles intermedia PLD (PDB: 3RLH) to evaluate two alternative mechanisms-covalent and non-covalent-for headgroup cleavage. The covalent mechanism involves a nucleophilic attack on the substrate's P atom by catalytic histidine, forming a phosphohistidine intermediate. It was originally suggested that this intermediate hydrolyzes, leading to linear phosphates. The non-covalent mechanism relies on the substrate's hydroxyl group performing an intramolecular attack on the P atom, thereby generating a cyclic phosphate. Structural refinement of the crystal structure revealed a cyclic phosphate bound at the active sit

SUBMITTER: Gismene C 

PROVIDER: S-EPMC11945750 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature