Crystal structure of vespid phospholipase A1 reveals insights into the mechanism for cause of membrane dysfunction
| Autor: | Yan-Ping Shih, Chien-Ying Chuang, Tzu-Ping Ko, Chia-Cheng Chou, Andrew H.-J. Wang, Nien-Jen Hu, Ming-Hon Hou, Chewn-Lang Ho |
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| Rok vydání: | 2016 |
| Předmět: |
Models
Molecular 0301 basic medicine Protein Conformation Stereochemistry Molecular Sequence Data Wasps Phospholipid Wasp Venoms Crystallography X-Ray Hemolysis Biochemistry Cell membrane Structure-Activity Relationship 03 medical and health sciences chemistry.chemical_compound Protein structure Phospholipase A1 Catalytic Domain Hydrolase medicine Animals Humans Amino Acid Sequence Lipase Molecular Biology Phospholipids Phospholipase A biology Chemistry Hydrolysis Cell Membrane Active site Phospholipases A1 030104 developmental biology medicine.anatomical_structure Insect Science biology.protein |
| Zdroj: | Insect Biochemistry and Molecular Biology. 68:79-88 |
| ISSN: | 0965-1748 |
| DOI: | 10.1016/j.ibmb.2015.11.002 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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