Crystal structure of vespid phospholipase A1 reveals insights into the mechanism for cause of membrane dysfunction

Ming Hon Hou, Chien Ying Chuang, Tzu Ping Ko, Nien Jen Hu, Chia Cheng Chou, Yan Ping Shih, Chewn Lang Ho, Andrew H.J. Wang

Research output: Contribution to journalArticlepeer-review

16 Citations (Scopus)

Abstract

Vespid phospholipase A1 (vPLA1) from the black-bellied hornet (Vespa basalis) catalyzes the hydrolysis of emulsified phospholipids and shows potent hemolytic activity that is responsible for its lethal effect. To investigate the mechanism of vPLA1 towards its function such as hemolysis and emulsification, we isolated vPLA1 from V. basalis venom and determined its crystal structure at 2.5 Å resolution. vPLA1 belongs to the α/β hydrolase fold family. It contains a tightly packed β-sheet surrounded by ten α-helices and a Gly-X-Ser-X-Gly motif, characteristic of a serine hydrolyase active site. A bound phospholipid was modeled into the active site adjacent to the catalytic Ser-His-Asp triad indicating that Gln95 is located at hydrogen-bonding distance from the substrate's phosphate group. Moreover, a hydrophobic surface comprised by the side chains of Phe53, Phe62, Met91, Tyr99, Leu197, Ala167 and Pro169 may serve as the acyl chain-binding site. vPLA1 shows global similarity to the N-terminal domain of human pancreatic lipase (HPL), but with some local differences. The lid domain and the β9 loop responsible for substrate selectivity in vPLA1 are shorter than in HPL. Thus, solvent-exposed hydrophilic residues can easily accommodate the polar head groups of phospholipids, thereby accounting for the high activity level of vPLA1. Our result provides a potential explanation for the ability of vPLA1 to hydrolyze phospholipids of cell membrane.

Original languageEnglish
Pages (from-to)79-88
Number of pages10
JournalInsect Biochemistry and Molecular Biology
Volume68
DOIs
Publication statusPublished - Jan 1 2016
Externally publishedYes

Keywords

  • Hornet venom
  • Lipase
  • Membrane dysfunction
  • Phospholipase A
  • Phospholipid hydrolysis
  • X-ray crystallography

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Insect Science

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