δ-Conotoxin Structure/Function through a Cladistic Analysis
| العنوان: | δ-Conotoxin Structure/Function through a Cladistic Analysis |
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| المؤلفون: | Richard DeLaCruz, Aryan Azimi-Zonooz, Peter J. West, Grzegorz Bulaj, Maren Watkins, Baldomero M. Olivera, Doju Yoshikami |
| المصدر: | Biochemistry. 40:13201-13208 |
| بيانات النشر: | American Chemical Society (ACS), 2001. |
| سنة النشر: | 2001 |
| مصطلحات موضوعية: | Delta, DNA, Complementary, animal structures, genetic structures, Molecular Sequence Data, Action Potentials, Mollusk Venoms, complex mixtures, Biochemistry, Sodium Channels, Cone snail, Mice, Structure-Activity Relationship, Conus, Animals, Amino Acid Sequence, Conotoxin, Cloning, Molecular, Conserved Sequence, Binding Sites, Sequence Homology, Amino Acid, biology, Chemistry, Sodium channel, Rana pipiens, Structure function, musculoskeletal system, biology.organism_classification, Sciatic Nerve, Cladistics, Electrophysiology, nervous system, Biophysics, Conotoxins, Ion Channel Gating, Sodium Channel Blockers |
| الوصف: | Delta-conotoxins are Conus peptides that inhibit inactivation of voltage-gated sodium channels. The suggestion that delta-conotoxins might be an essential component of the venoms of fish-hunting cone snails which rapidly immobilize their prey [Terlau, H., Shon, K., Grilley, M., Stocker, M., Stühmer, W., and Olivera, B. M. (1996) Nature 381, 148-151] has not been tested. On the basis of cDNA cloning, all of the fish-hunting Conus analyzed yielded at least one delta-conotoxin sequence. In addition, one delta-conotoxin isolated from the venom of Conus striatus had an amino acid sequence identical to that predicted from cDNA cloning. This new peptide exhibited properties of delta-conotoxins: it targeted sodium channels and potentiated action potentials by slowing channel inactivation. Homologous sequences of delta-conotoxins from two groups (clades) of related fish-hunting Conus species share consensus features but differ significantly from the two known delta-conotoxins from mollusc-hunting Conus venoms. Three large hydrophobic amino acids were conserved; analogues of the previously described delta-conotoxin PVIA with alanine substituted for the conserved amino acids F9 and I12 lost substantial biological activity. In contrast, both the T8A and K13A delta-conotoxin PVIA analogues, where substitutions were at nonconserved loci, proved to be biologically active. Taken together, our results indicate that a cladistic approach can identify amino acids critical for the activity of conotoxins and provide extensive information as to which amino acid substitutions can be made without significant functional consequences. |
| تدمد: | 1520-4995 0006-2960 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8a9f5731456916768b2e2d5cc4bd4cafTest https://doi.org/10.1021/bi010683aTest |
| رقم الانضمام: | edsair.doi.dedup.....8a9f5731456916768b2e2d5cc4bd4caf |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15204995 00062960 |
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