Primary structures of four trypsin inhibitor E homologs from venom of Dendroaspis angusticeps: structure–function comparisons with other dendrotoxin homologs

• Published in: Toxicon (Oxford) Vol. 40; no. 3; pp. 297 - 308
• Main Authors: Sigle, Randy, Hackett, Murray, Aird, Steven D.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01.03.2002; Elsevier Science
• Subjects: Amino Acid Sequence; Animal poisons toxicology. Antivenoms; Animals; Biological and medical sciences; Brain; Chromatography, Liquid; Dendroaspis angusticeps; dendrotoxin; Elapid venoms; Elapid Venoms - chemistry; Elapidae; Epsilon-dendrotoxins; Mambas; Mass Spectrometry; Medical sciences; Molecular Sequence Data; Potassium channels; Potassium Channels - drug effects; Protease inhibitors; Protease Inhibitors - metabolism; Rats; Structure-Activity Relationship; Synaptosomes; Toxicology; Toxins; Trypsin Inhibitors - chemistry; Trypsin Inhibitors - metabolism; Epsilon-dendrotoxins; Toxins; Potassium channels; Mambas; Protease inhibitors; Elapid venoms; Rat; Molecular structure; Potassium ion; Toxicity; Ionic channel; Synaptosome; Structure activity relation; Aminoacid sequence; Serine endopeptidases; Enzyme; Nomenclature; Rodentia; Enzyme inhibitor; Animal origin; Primary structure; Ophidia; Peptidases; Toxin; Vertebrata; Trypsin; Mammalia; Polypeptide; Animal; Venom; Hydrolases; Reptilia; Structural analysis
• ISSN: 0041-0101; 1879-3150
• DOI: 10.1016/S0041-0101(01)00227-6

Four trypsin inhibitor homologs, the first known from Dendroaspis angusticeps venom, were characterized using a combination of gel filtration, cation exchange, reverse-phase liquid chromatography, Edman degradation and mass spectrometry. The four toxins comprise two 57 residue and two 59 residue isoforms. The long toxins possess a Lys–Gln N-terminal extension lacked by the short toxins. The only other structural difference is an Arg/His replacement at position 55. The long Arg55 variant is identical to trypsin inhibitor E from the venom of Dendroaspis polylepis. The name ϵ-dendrotoxin is suggested so as to follow the nomenclature of Benishin, C.G., Sorensen, R.G., Brown, W.E., Krueger, B.K., Blaustein, M.P., 1988. Four polypeptide components of green mamba venom selectively block certain potassium channels in rat brain synaptosomes. Mol. Pharmacol. 34, 152–159. Among snake venom protease inhibitors, the ϵ-dendrotoxins are structurally most like the δ-dendrotoxins, with which they share only 64% of their residues. In addition, the ϵ-dendrotoxins display hydropathy profiles more like those of the α- and δ-dendrotoxins, than those of the trypsin inhibitors from snake venoms. Given the strong protease inhibitory activity of trypsin inhibitor E and the recently demonstrated weak K + channel inhibitory activity of two of these variants (Tytgat, J., Vandenberghe, I., Ulens, C., Van Beeumen, J., 2001. New polypeptide components purified from mamba venom. FEBS Lett. 491, 217–221), the ϵ-dendrotoxins represent structural and functional intermediates between the facilitatory toxins and the protease inhibitors.