Determinants of pH profile and acyl chain selectivity in lysosomal phospholipase A2 [S]
V Hinkovska-Galcheva, R Kelly, KA Manthei… - Journal of Lipid …, 2018 - ASBMB
Lysosomal phospholipase A2 (LPLA 2) is characterized by broad substrate recognition,
peak activity at acidic pH, and the transacylation of lipophilic alcohols, especially N-acetyl-
sphingosine. Prior structural analysis of LPLA 2 revealed the presence of an atypical acidic
residue, Asp13, in the otherwise hydrophobic active site cleft. We hypothesized that Asp13
contributed to the pH profile and/or substrate preference of LPLA 2 for unsaturated acyl
chains. To test this hypothesis, we substituted Asp13 for alanine, cysteine, or phenylalanine; …
peak activity at acidic pH, and the transacylation of lipophilic alcohols, especially N-acetyl-
sphingosine. Prior structural analysis of LPLA 2 revealed the presence of an atypical acidic
residue, Asp13, in the otherwise hydrophobic active site cleft. We hypothesized that Asp13
contributed to the pH profile and/or substrate preference of LPLA 2 for unsaturated acyl
chains. To test this hypothesis, we substituted Asp13 for alanine, cysteine, or phenylalanine; …
