title: Crystal structure of phospholipase PA2-Vb, a protease-activated receptor agonist from the Trimeresurus stejnegeri snake venom.
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 (IP3R) and induces mouse aorta contraction. PAR-1, phospholipase C and IP3R 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.
authors.affiliation: Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230026, People's Republic of China.
authors.forename: Fuxing
authors.initials: F
authors.lastname: Zeng
authors.affiliation: Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230026, People's Republic of China.
authors.forename: Wenjuan
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Physiology, Anhui Medical University, Hefei, Anhui 230032, People's Republic of China.
authors.forename: Nairui
authors.initials: N
authors.lastname: Xue
authors.affiliation: Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230026, People's Republic of China.
authors.forename: Maikun
authors.initials: M
authors.lastname: Teng
authors.affiliation: Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230026, People's Republic of China. Electronic address: sachem@ustc.edu.cn.
authors.forename: Xu
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Physiology, Anhui Medical University, Hefei, Anhui 230032, People's Republic of China. Electronic address: shenbing@ahmu.edu.cn.
authors.forename: Bing
authors.initials: B
authors.lastname: Shen
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002118:Calcium / Q000378:metabolism; D003435:Crotalid Venoms / Q000201:enzymology*; D018360:Crystallography, X-Ray; D006863:Hydrogen-Ion Concentration; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D054467:Phospholipases A2 / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D044462:Receptors, Proteinase-Activated / Q000819:agonists*; D017841:Trimeresurus; D014661:Vasoconstriction / Q000187:drug effects
chemical_list: D003435:Crotalid Venoms; D044462:Receptors, Proteinase-Activated; D054467:Phospholipases A2; D002118:Calcium
keywords: Acidic phospholipase A(2); Ca(2+) release; Crystal structure; IP(3) receptor; Vasoconstrictor activity