6MQD

Myotoxin II from Bothrops moojeni complexed with Rosmarinic Acid

Summary for 6MQD

• Entry DOI: 10.2210/pdb6mqd/pdb
• Descriptor: Basic phospholipase A2 homolog 2, (2R)-3-(3,4-dihydroxyphenyl)-2-{[(2E)-3-(3,4-dihydroxyphenyl)prop-2-enoyl]oxy}propanoic acid (3 entities in total)
• Functional Keywords: rosmarinic acid, snake venom, toxin
• Biological source: Bothrops moojeni (Lance-headed viper)
• Total number of polymer chains: 2
• Total formula weight: 28184.74

Authors

Salvador, G.H.M.,Fontes, M.R.M. (deposition date: 2018-10-09, release date: 2019-03-20, Last modification date: 2024-10-30)

Primary citation

Salvador, G.H.M.,Cardoso, F.F.,Gomes, A.A.,Cavalcante, W.L.G.,Gallacci, M.,Fontes, M.R.M.
Search for efficient inhibitors of myotoxic activity induced by ophidian phospholipase A2-like proteins using functional, structural and bioinformatics approaches.
Sci Rep, 9:510-510, 2019

PubMed Abstract: Ophidian accidents are considered an important neglected tropical disease by the World Health Organization. Particularly in Latin America, Bothrops snakes are responsible for the majority of the snakebite envenomings that are not efficiently treated by conventional serum therapy. Thus, the search for simple and efficient inhibitors to complement this therapy is a promising research area, and a combination of functional and structural assays have been used to test candidate ligands against specific ophidian venom compounds. Herein, we tested a commercial drug (acetylsalicylic acid, ASA) and a plant compound with antiophidian properties (rosmarinic acid, RA) using myographic, crystallographic and bioinformatics experiments with a phospholipase A-like toxin, MjTX-II. MjTX-II/RA and MjTX-II/ASA crystal structures were solved at high resolution and revealed the presence of ligands bound to different regions of the toxin. However, in vitro myographic assays showed that only RA is able to prevent the myotoxic effects of MjTX-II. In agreement with functional results, molecular dynamics simulations showed that the RA molecule remains tightly bound to the toxin throughout the calculations, whereas ASA molecules tend to dissociate. This approach aids the design of effective inhibitors of PLA-like toxins and, eventually, may complement serum therapy.

PubMed: 30679550
DOI: 10.1038/s41598-018-36839-6

Experimental method

X-RAY DIFFRACTION (1.6 Å)