3UX7

Crystal structure of a dimeric myotoxic component of the Vipera ammodytes meridionalis venom reveals determinants of myotoxicity and membrane damaging activity

Summary for 3UX7

• Entry DOI: 10.2210/pdb3ux7/pdb
• Descriptor: Ammodytin L(1) isoform, SULFATE ION (3 entities in total)
• Functional Keywords: toxin, snake venom, ser49 myotoxin
• Biological source: Vipera ammodytes meridionalis
• Total number of polymer chains: 8
• Total formula weight: 109581.09

Authors

Georgieva, D.,Coronado, M.,Oberthuer, D.,Buck, F.,Duhalov, D.,Arni, R.K.,Genov, N.,Betzel, C. (deposition date: 2011-12-04, release date: 2012-04-25, Last modification date: 2024-10-16)

Primary citation

Georgieva, D.,Coronado, M.,Oberthur, D.,Buck, F.,Duhalov, D.,Arni, R.K.,Betzel, C.
Crystal structure of a dimeric Ser49 PLA(2)-like myotoxic component of the Vipera ammodytes meridionalis venomics reveals determinants of myotoxicity and membrane damaging activity.
Mol Biosyst, 8:1405-1411, 2012

PubMed Abstract: Myotoxicity and membrane damage play a central role in the life-threatening effects of the viper envenomation. Myotoxins are an important part of the viper venomics. A Ser49 PLA₂-like myotoxin from the venom of Vipera ammodytes meridionalis, the most venomous snake in Europe, was crystallized and its three-dimensional structure determined. The toxin is devoid of phospholipolytic activity. The structure demonstrates a formation of dimers. In the dimers functionally important peptide segments, located on the protein surface, point in the same direction which can strengthen the pharmacological effect. This supports the hypothesis about the physiological importance of the toxin oligomerization for the myotoxicity and membrane damage. The crystallographic model revealed that the structural determinants of myotoxicity (a positively charged C-terminal region and a hydrophobic knuckle) are fully exposed on the protein surface and accessible for interactions with target membranes. Distortion of the catalytic site region explains the absence of enzymatic activity. The structure reveals anion-binding sites which can be considered as possible sites of interactions of the toxin with a negatively charged membrane surface. The high structural similarity of the Ser49 myotoxin and Asp49 PLA₂ from the same venom suggests an evolutionary relationship: probably, the Ser49 myotoxin is a product of evolution of the catalytically active phospholipase A₂. The first toxin lost the enzymatic activity which is not necessary for the myotoxicity but preserved the cytotoxicity and membrane damaging activity as important components of the venom toxicity.

PubMed: 22362132
DOI: 10.1039/c2mb05490f

Experimental method

X-RAY DIFFRACTION (2.97 Å)