Current Protein & Peptide Science

Ben M. Dunn  
Department of Biochemistry and Molecular Biology University of Florida
College of Medicine, P.O. Box 100245, Gainesville
Florida, FL 32610-0245
USA

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Structure and Dynamics of Cardiotoxins

Author(s): Anastasia G. Konshina, Peter V. Dubovskii and Roman G. Efremov

Affiliation: Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 16/10 Miklukho-Maklaya str., 117997 GSP, Moscow V-437, Russia.

Abstract:

Cytotoxins (or cardiotoxins; CTs) are toxins from cobra venom characterized by the three-finger (TF) fold. CTs are on average 60-residue-long peptides, possessing as many as 4 disulfide bonds. The elements of antiparallel β-structure take origin from the hydrophobic core formed by the disulfides. The β-strands adopt the shape of the three loops, giving the name of the fold. While neurotoxins (NTs) - also TF proteins from snake venom - exert their effect through specific interactions with protein receptors, no specific protein target has been found for CTs. Unlike NTs, CTs are amphiphilic and cytotoxic against a variety of cells, including cancer ones. Thus, the hypothesis that the activity of CTs is caused by their interactions with lipid membranes is currently central. To understand molecular basis behind variations in toxicities of CTs highly homologous in their sequences, detailed knowledge of their structure and dynamics is required. The present review summarizes experimental and computational data on the spatial organization of CTs and their dynamics in various environments (aqueous solution, membranous milieus).

Keywords: Cardiotoxin, disulfide-rich protein, three-finger toxin, membrane-mimetic environment, molecular modeling, spatial structure and dynamics, normal mode analysis, spatial structure and dynamics, Elapidae snake, Pharmacological characteristics, Naja pallida

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Article Details

VOLUME: 13
ISSUE: 6
Page: [570 - 584]
Pages: 15
DOI: 10.2174/138920312803582960
Price: $58