Abstract
The amino acid sequences of four presynaptically active toxins from mamba snake venom (termed ‘dendrotoxins’) were compared systematically with homologous sequences of members of the proteinase inhibitor family (Kunitz). A comparison based on the complete sequences revealed that relatively few amino acid changes are necessary to abolish antiprotease activity and convert a proteinase inhibitor into a dendrotoxin. When comparison centred only on the sequence segments known to comprise the antiprotease site of bovine pancreatic trypsin inhibitor, the dendrotoxins were clearly classified apart from all the known inhibitors. Since the mode of action of the bovine pancreatic trypsin/kallikrein inhibitor involves β sheet formation with the enzyme, predictions were obtained for this secondary structure in the region of the ‘antiprotease site’ throughout the homologues. Again, the dendrotoxins were clearly distinguished from the inhibitors.Structure/activity analyses, based on the crystal structures of inhibitor/enzyme complexes, suggest that unlike proteinase inhibitors, dendrotoxins might specifically co‐ordinate the active‐site ‘catalytic’ histidine residues of serine proteases. Although the significance of this remains to be studied, the presynaptic target is expected to involve an as yet uncharacterised member of the serine protease family.
References
26
Referenced
79
10.3109/15569548409097923
10.1146/annurev.bi.49.070180.003113
10.1007/978-3-642-87966-1_55
10.1016/0022-2836(78)90246-2
10.1016/0022-2836(83)90078-5
10.1016/0167-4838(83)90067-5
{'key': 'e_1_2_3_8_2', 'first-page': '721', 'volume': '76', 'author': 'Takahashi H.', 'year': '1974', 'journal-title': 'J. Biochem. (Tokyo)'}
/ J. Biochem. (Tokyo) by Takahashi H. (1974)10.1016/S0076-6879(81)80063-8
{'key': 'e_1_2_3_10_2', 'first-page': '832', 'volume': '38', 'author': 'Kato I.', 'year': '1979', 'journal-title': 'Fed. Proc.'}
/ Fed. Proc. by Kato I. (1979)10.1111/j.1432-1033.1975.tb02391.x
10.1016/0014-5793(80)80997-5
10.1016/S0076-6879(76)45074-7
10.1515/bchm2.1979.360.2.1297
{'key': 'e_1_2_3_15_2', 'volume-title': 'Numerical taxonomy', 'author': 'Sneath P. H.', 'year': '1973'}
/ Numerical taxonomy by Sneath P. H. (1973)10.1107/S0567740875002415
10.1021/bi00699a002
10.1021/bi00613a026
10.1016/0022-2836(77)90095-X
{'key': 'e_1_2_3_20_2', 'first-page': '67', 'volume': '4', 'author': 'Fitch W. M.', 'year': '1970', 'journal-title': 'Evol. Biol.'}
/ Evol. Biol. by Fitch W. M. (1970)10.1093/oxfordjournals.jbchem.a131881
10.1016/0022-2836(77)90207-8
10.1016/0022-2836(82)90498-3
10.1111/j.1432-1033.1983.tb07848.x
{'key': 'e_1_2_3_25_2', 'first-page': '409', 'volume': '168', 'author': 'Hollecker M.', 'year': '1983', 'journal-title': 'J. Biol.'}
/ J. Biol. by Hollecker M. (1983){'key': 'e_1_2_3_26_2', 'first-page': '222', 'volume': '79', 'author': 'Harvey A. L.', 'year': '1984', 'journal-title': 'J. Physiol. (Paris)'}
/ J. Physiol. (Paris) by Harvey A. L. (1984)10.1016/B978-0-12-588250-7.50008-7
Dates
Type | When |
---|---|
Created | 20 years, 6 months ago (March 3, 2005, 7:14 p.m.) |
Deposited | 1 year, 9 months ago (Nov. 23, 2023, 8:19 a.m.) |
Indexed | 1 month ago (Aug. 2, 2025, 1:23 a.m.) |
Issued | 39 years, 9 months ago (Dec. 1, 1985) |
Published | 39 years, 9 months ago (Dec. 1, 1985) |
Published Online | 20 years, 6 months ago (March 3, 2005) |
Published Print | 39 years, 9 months ago (Dec. 1, 1985) |
@article{DUFTON_1985, title={Proteinase inhibitors and dendrotoxins: Sequence classification, structural prediction and structure/activity}, volume={153}, ISSN={1432-1033}, url={http://dx.doi.org/10.1111/j.1432-1033.1985.tb09349.x}, DOI={10.1111/j.1432-1033.1985.tb09349.x}, number={3}, journal={European Journal of Biochemistry}, publisher={Wiley}, author={DUFTON, Mark J.}, year={1985}, month=dec, pages={647–654} }