NMR of conotoxins: structural features and an analysis of chemical shifts of post-translationally modified amino acids

Marx, Ute C.; Daly, Norelle L.; Craik, David J.

doi:10.1002/mrc.1821

Cited by 43 publications

(27 citation statements)

References 76 publications

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“…1D). These negative ␣H secondary shifts indicate a helical region, which is consistent with the previously reported three-dimensional structure of native AuIB (21) and other ␣-conotoxin structures reported to date (37). Interestingly, NMR secondary shift data for [Y5A]AuIB and [N12A]AuIB were more consistent with the ribbon isomer of AuIB (21) despite using a regioselective disulfide bond formation strategy to form the native (globular) isomer (Fig.…”

Section: Alanine Scanning Mutagenesis Identifies Residues In the Auibsupporting

confidence: 80%

Identifying Key Amino Acid Residues That Affect α-Conotoxin AuIB Inhibition of α3β4 Nicotinic Acetylcholine Receptors

Grishin

Cuny

Hung

et al. 2013

Journal of Biological Chemistry

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Background: ␣-Conotoxin AuIB interacts with ␣3␤4 nAChRs and GABA B receptors, but structural determinants of these interactions are unknown. Results: Using alanine scanning mutagenesis and molecular dynamics, we identified residues crucial for AuIB⅐␣3␤4 nAChR interaction. Conclusion:We identified the key residues that mediate AuIB⅐␣3␤4 nAChR interaction. Significance: Ability to direct ␣-conotoxin binding to nAChRs or GABA B receptors will improve analgesic conopeptides.

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Section: Alanine Scanning Mutagenesis Identifies Residues In the Auibsupporting

confidence: 80%

Identifying Key Amino Acid Residues That Affect α-Conotoxin AuIB Inhibition of α3β4 Nicotinic Acetylcholine Receptors

Grishin

Cuny

Hung

et al. 2013

Journal of Biological Chemistry

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“…In general, the PTMs of amino acids extends the range of biological functions of the protein; for example, glycosylation helps in providing structural components, modifying physiological properties, mediating & modulating cell-adhesion and signaling [30,31]. In case of conotoxins, the PTMs of amino acids increase the toxin potency [24,25,32,33] and stabilize the three-dimensional structure of the peptide [34][35][36]. Thus, glycosylation may increase lifespan of peptides by stabilizing the structural conformation and slowing down its proteolytic degradation.…”

Section: Post-translational Modificationmentioning

confidence: 99%

Conotoxins: Structure, Therapeutic Potential and Pharmacological Applications

Mir¹,

Karim²,

Kamal³

et al. 2016

CPD

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Cone snails, also known as marine gastropods, from Conus genus produce in their venom a diverse range of small pharmacologically active structured peptides called conotoxins. The cone snail venoms are widely unexplored arsenal of toxins with therapeutic and pharmacological potential, making them a treasure trove of ligands and peptidic drug leads. Conotoxins are small disulphide bonded peptides which act as remarkable selective inhibitors and modulators of ion channels (calcium, sodium, potassium), nicotinic acetylcholine receptors, noradrenaline transporters, N-methyl-D-aspartate receptors, and neurotensin receptors. They are highly potent and specific against several neuronal targets making them valuable as research tools, drug leads and even therapeutics. In this review we discuss their gene superfamily classification, nomenclature, post-translational modification, structural framework, pharmacology and medical applications of the active conopeptides. We aim to give an overview of their structure and therapeutic potential. Understanding these aspects of conopeptides will help in designing more specific peptidic analogues.

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“…Once the activity of Lo1a had been determined, we employed NMR-based techniques to elucidate the structure of this novel peptide. According to Marx et al (46), NMR is the method of choice for determining conotoxin structures, because conotoxins are generally difficult to crystallize and are not amenable to x-ray methods, with a few exceptions such as PnIA and PnIB (47,48). ␣-Conotoxin Lo1a was shown to be highly soluble, and NMR spectra were readily assigned and used to generate a high resolution structure.…”

Section: Discussionmentioning

confidence: 99%

Structure-Function Elucidation of a New α-Conotoxin, Lo1a, from Conus longurionis

Lebbe

Peigneur

Maiti

et al. 2014

Journal of Biological Chemistry

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Background: ␣-Conotoxins are small toxins produced by cone snails and antagonists of nicotinic acetylcholine receptors. Results: Two mutants were created to investigate the unusual C terminus of a novel ␣-conotoxin from Conus longurionis. Conclusion: We characterized an important residue for discrimination between neuronal and muscle subtype nicotinic acetylcholine receptors. Significance: This opens perspectives for designing new ligands to affect brain disorders.

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NMR of conotoxins: structural features and an analysis of chemical shifts of post-translationally modified amino acids

Cited by 43 publications

References 76 publications

Identifying Key Amino Acid Residues That Affect α-Conotoxin AuIB Inhibition of α3β4 Nicotinic Acetylcholine Receptors

Identifying Key Amino Acid Residues That Affect α-Conotoxin AuIB Inhibition of α3β4 Nicotinic Acetylcholine Receptors

Conotoxins: Structure, Therapeutic Potential and Pharmacological Applications

Structure-Function Elucidation of a New α-Conotoxin, Lo1a, from Conus longurionis

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