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7rjz

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

Structural highlights

7rjz is a 2 chain structure with sequence from Bothrops jararacussu. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.7Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

PA2B2_BOTJR Snake venom phospholipase A2 (PLA2) that shows a moderate enzymatic activity. It induces indirect hemolytic, anticoagulant, and cytotoxic activities. In vivo, it induces muscle necrosis, accompanied by polymorphonuclear cell infiltration, and edema in the mouse paw. PLA2 catalyzes the calcium-dependent hydrolysis of the 2-acyl groups in 3-sn-phosphoglycerides.^[1] ^[2]

Publication Abstract from PubMed

Phospholipases A2 (PLA2s) are found in almost every venomous snake family. In snakebites, some PLA2s 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 PLA2 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 PLA2-like proteins.

BthTX-II from Bothrops jararacussu venom has variants with different oligomeric assemblies: An example of snake venom phospholipases A2 versatility.,Borges RJ, Salvador GHM, Campanelli HB, Pimenta DC, de Oliveira Neto M, Uson I, Fontes MRM Int J Biol Macromol. 2021 Nov 30;191:255-266. doi:, 10.1016/j.ijbiomac.2021.09.083. Epub 2021 Sep 20. PMID:34547312^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Pereira MF, Novello JC, Cintra AC, Giglio JR, Landucci ET, Oliveira B, Marangoni S. The amino acid sequence of bothropstoxin-II, an Asp-49 myotoxin from Bothrops jararacussu (Jararacucu) venom with low phospholipase A2 activity. J Protein Chem. 1998 May;17(4):381-6. PMID:9619591
↑ Andriao-Escarso SH, Soares AM, Rodrigues VM, Angulo Y, Diaz C, Lomonte B, Gutierrez JM, Giglio JR. Myotoxic phospholipases A(2) in bothrops snake venoms: effect of chemical modifications on the enzymatic and pharmacological properties of bothropstoxins from Bothrops jararacussu. Biochimie. 2000 Aug;82(8):755-63. PMID:11018293
↑ Borges RJ, Salvador GHM, Campanelli HB, Pimenta DC, de Oliveira Neto M, Usón I, Fontes MRM. 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. 2021 Nov 30;191:255-266. PMID:34547312 doi:10.1016/j.ijbiomac.2021.09.083