Crystal structure of phospholipase PA2‐Vb, a protease‐activated receptor agonist from the Trimeresurus stejnegeri snake venom. Issue 24 (4th November 2014)

• Record Type: Journal Article
• Authors: Zeng, Fuxing; Zhang, Wenjuan; Xue, Nairui; Teng, Maikun; Li, Xu; Shen, Bing
• Is Part Of: FEBS letters. Volume 588:Issue 24(2014)
• Page Start: 4604
• Page End: 4612
• Publication Date: 2014-11-04
• Subjects: PLA2 -- phospholipases A2 -- PAR-1 -- protease-activated receptor 1 -- IP3R -- inositol 1, 4, 5-trisphosphate receptor -- svPLA2 -- snake venom PLA2 -- VSMCs -- vascular smooth muscle cells -- SR -- sarcoplasmic reticulum -- RyR -- ryanodine receptor -- GPCRs -- G-protein coupled receptors -- RP -- reversible permeabilization -- pBPB -- p-bromofenacil bromide -- 2-APB -- 2-aminoethoxy diphenyl borate -- PLCβ -- phospholipase Cβ -- Acidic phospholipase A2 -- Vasoconstrictor activity -- Ca2+ release -- IP3 receptor -- Crystal structure; Biochemistry -- Periodicals; Biophysics -- Periodicals; Molecular biology -- Periodicals; Biochimie -- Périodiques; Biochemistry; Biophysics; Molecular biology; Periodicals; 572.05
• DOI: 10.1016/j.febslet.2014.10.032
• Languages: English
• ISSNs: 0014-5793

Abstract

Abstract : Phospholipase A2 (PLA2 ) is an important component in snake venoms. Here, an acidic PLA2, designated PA2‐Vb was isolated from the Trimeresurus stejnegeri snake venom. PA2‐Vb acts on a protease‐activated receptor (PAR‐1) to evoke Ca 2+ release through the inositol 1, 4, 5‐trisphosphate receptor (IP3 R) and induces mouse aorta contraction. PAR‐1, phospholipase C and IP3 R inhibitors suppressed PA2‐Vb‐induced aorta contraction. The crystal structure reveals that PA2‐Vb has the typical fold of most snake venom PLA2 . Several PEG molecules bond to a positively charged pocket. The finding offers a novel pharmacological basis of the structure for investigating the PAR‐1 receptor and suggests potential applications for PA2‐Vb in the vascular system.