Primary structures of four trypsin inhibitor E homologs from venom of Dendroaspis angusticeps: structure-function comparisons with other dendrotoxin homologs.
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 epsilon-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 epsilon-dendrotoxins are structurally most like the delta-dendrotoxins, with which they share only 64% of their residues. In addition, the epsilon-dendrotoxins display hydropathy profiles more like those of the alpha- and delta-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 epsilon-dendrotoxins represent structural and functional intermediates between the facilitatory toxins and the protease inhibitors.
Sigle
Randy
R
Department of Medicinal Chemistry, Health Sciences Building, H172D, Box 357610, University of Washington, Seattle, WA 98195-7610, USA.
Hackett
Murray
M
Aird
Steven D
SD
D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain; D002853:Chromatography, Liquid; D004546:Elapid Venoms / Q000737:chemistry*; D017815:Elapidae; D013058:Mass Spectrometry; D008969:Molecular Sequence Data; D015221:Potassium Channels / Q000187:drug effects; D011480:Protease Inhibitors / Q000378:metabolism; D051381:Rats; D013329:Structure-Activity Relationship; D013574:Synaptosomes; D014361:Trypsin Inhibitors / Q000737:chemistry* / Q000378:metabolism
D004546:Elapid Venoms; D015221:Potassium Channels; D011480:Protease Inhibitors; D014361:Trypsin Inhibitors; C020273:dendrotoxin