Snakes are among the most successful groups of reptiles, numbering about 3,000 extant species. In spite of centuries of comparative anatomical and morphological studies, many aspects of snake systematics remain unsolved. To better understand the evolution and diversity of genomic characteristics in Serpentes, we analyzed online sequence data of mitochondrial and nuclear genes, as well as cytogenetic data and reviewed other genomic characteristics such as toxin genes. After the analysis of the whole-genome and chromosomal organization, we find that: (1) cytogenetic comparisons could provide a useful tool to investigate intergeneric and tribal relationships within the extremely diverse neotropical xenodontine snakes; (2) toxin genes could also help to understand snake evolution if special care is taken to choose the sequences because of the difficulty in avoiding paralogs; (3) snake phylogeny based on mitochondrial genome sequences is largely consistent with the relationship obtained using nuclear genes.

Crotamine, a myotoxin from the venom of South American rattlesnake, is structurally related to b-defensins, antimicrobial peptides (AMPs) found in vertebrate animals. Here, we tested the antibacterial properties of crotamine and found that it killed several strains of Escherichia coli, with the MICs ranging from 25 to 100 lg ml À1 . Time-kill and bacterial membrane permeabilization assays revealed that killing of bacteria by crotamine occurred within 1 h and reached the maximum by 2 h. Additionally, the anti-E. coli activity of crotamine was completely abolished with 12.5 mM NaCl. Furthermore, the three intramolecular disulfide bonds of crotamine appeared dispensable for its antibacterial activity. The reduced form of crotamine was active against E. coli as well. However, crotamine showed no or weak activity up to 200 lg ml À1 against other species of Gram-negative and Gram-positive bacteria. Crotamine showed no appreciable hemolytic activity to erythrocytes. Our studies revealed that crotamine is also an AMP that kills bacteria through membrane permeabilization. However, crotamine appears to have a narrow antibacterial spectrum, distinct from many classical b-defensins, reinforcing the notion that crotamine originated from the b-defensin gene lineage, but has undergone significant functional diversification.

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Crotamine, a 5-kDa peptide, possesses a unique biological versatility. Not only has its cell-penetrating activity become of clinical interest but, moreover, its potential selective antitumor activity is of great pharmacological importance. In the past, several studies have attempted to elucidate the exact molecular target responsible for the crotamine-induced skeletal muscle spasm. The aim of this study was to investigate whether crotamine affects voltagegated potassium (K V ) channels in an effort to explain its in vivo effects. Crotamine was studied on ion channel function using the two-electrode voltage clamp technique on 16 cloned ion channels (12 K V channels and 4 Na V channels), expressed in Xenopus laevis oocytes. Crotamine selectively inhibits K V 1.1, K V 1.2, and K V 1.3 channels with an IC 50 of ϳ300 nM, and the key amino acids responsible for this molecular interaction are suggested. Our results demonstrate for the first time that the symptoms, which are observed in the typical crotamine syndrome, may result from the inhibition of K V channels. The ability of crotamine to inhibit the potassium current through K V channels unravels it as the first snake peptide with the unique multifunctionality of cell-penetrating and antitumoral activity combined with K V channel-inhibiting properties. This new property of crotamine might explain some experimental observations and opens new perspectives on pharmacological uses.

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