6TMY

Crystal structure of isoform CBd of the basic phospholipase A2 subunit of crotoxin from Crotalus durissus terrificus

Summary for 6TMY

• Entry DOI: 10.2210/pdb6tmy/pdb
• Descriptor: Phospholipase A2 crotoxin basic subunit CBc, SODIUM ION, TETRAETHYLENE GLYCOL, ... (5 entities in total)
• Functional Keywords: crotoxin, cb isoforms, presynaptic phospholipase a2, hydrolase
• Biological source: Crotalus durissus terrificus (tropical rattlesnake)
• Total number of polymer chains: 6
• Total formula weight: 88731.89

Authors

Nemecz, D.,Ostrowski, M.,Saul, F.A.,Faure, G. (deposition date: 2019-12-05, release date: 2020-12-02, Last modification date: 2024-10-09)

Primary citation

Nemecz, D.,Ostrowski, M.,Ravatin, M.,Saul, F.,Faure, G.
Crystal Structure of Isoform CBd of the Basic Phospholipase A 2 Subunit of Crotoxin: Description of the Structural Framework of CB for Interaction with Protein Targets.
Molecules, 25:-, 2020

PubMed Abstract: Crotoxin, from the venom of the South American rattlesnake is a potent heterodimeric presynaptic β-neurotoxin that exists in individual snake venom as a mixture of isoforms of a basic phospholipase A (PLA) subunit (CBa, CBb, CBc, and CBd) and acidic subunit (CA). Specific natural mutations in CB isoforms are implicated in functional differences between crotoxin isoforms. The three-dimensional structure of two individual CB isoforms (CBa, CBc), and one isoform in a crotoxin (CACBb) complex, have been previously reported. This study concerns CBd, which by interaction with various protein targets exhibits many physiological or pharmacological functions. It binds with high affinity to presynaptic receptors showing neurotoxicity, but also interacts with human coagulation factor Xa (hFXa), exhibiting anticoagulant effect, and acts as a positive allosteric modulator and corrector of mutated chloride channel, cystic fibrosis transmembrane conductance regulator (CFTR), implicated in cystic fibrosis. Thus, CBd represents a novel family of agents that have potential in identifying new drug leads related to anticoagulant and anti-cystic fibrosis function. We determined here the X-ray structure of CBd and compare it with the three other natural isoforms of CB. The structural role of specific amino acid variations between CB isoforms are analyzed and the structural framework of CB for interaction with protein targets is described.

PubMed: 33202772
DOI: 10.3390/molecules25225290

Experimental method

X-RAY DIFFRACTION (1.8 Å)