7RJZ

BthTX-II variant a, from Bothrops jararacussu venom, complexed with benzoic acid

Summary for 7RJZ

• Entry DOI: 10.2210/pdb7rjz/pdb
• Related: 7RJI
• Descriptor: BthTX-IIa, BENZOIC ACID (3 entities in total)
• Functional Keywords: basic phospholipase a2, bthtx-ii variant a, bothrops jararacussu, toxin
• Biological source: Bothrops jararacussu
• Total number of polymer chains: 2
• Total formula weight: 27719.91

Authors

Borges, R.J.,Fontes, M.R.M. (deposition date: 2021-07-21, release date: 2022-01-05, Last modification date: 2024-10-30)

Primary citation

Borges, R.J.,Salvador, G.H.M.,Campanelli, H.B.,Pimenta, D.C.,de Oliveira Neto, M.,Uson, I.,Fontes, M.R.M.
BthTX-II from Bothrops jararacussu venom has variants with different oligomeric assemblies: An example of snake venom phospholipases A 2 versatility.
Int.J.Biol.Macromol., 191:255-266, 2021

PubMed Abstract: Phospholipases A (PLAs) are found in almost every venomous snake family. In snakebites, some PLAs can quickly cause local myonecrosis, which may lead to permanent sequelae if antivenom is administered belatedly. They hydrolyse phospholipids in membranes through a catalytic calcium ions-dependent mechanism. BthTX-II is a basic PLA and the second major component in the venom of Bothrops jararacussu. Herein, using the software SEQUENCE SLIDER, which integrates crystallographic, mass spectrometry and genetic data, we characterized the primary, tertiary and quaternary structure of two BthTX-II variants (called a and b), which diverge in 7 residues. Crystallographic structure BthTX-IIa is in a Tense-state with its distorted calcium binding loop buried in the dimer interface, contrarily, the novel BthTX-IIb structure is a monomer in a Relax-state with a fatty acid in the hydrophobic channel. Structural data in solution reveals that both variants are monomeric in neutral physiological conditions and mostly dimeric in an acidic environment, being catalytic active in both situations. Therefore, we propose two myotoxic mechanisms for BthTX-II, a catalytic one associated with the monomeric assembly, whereas the other has a calcium independent activity related to its C-terminal region, adopting a dimeric conformation similar to PLA-like proteins.

PubMed: 34547312
DOI: 10.1016/j.ijbiomac.2021.09.083

Experimental method

X-RAY DIFFRACTION (1.7 Å)