3ZKT

SOLUTION STRUCTURE OF THE SOMATOSTATIN SST3 RECEPTOR ANTAGONIST TAU- CONOTOXIN CnVA

Summary for 3ZKT

• Entry DOI: 10.2210/pdb3zkt/pdb
• NMR Information: BMRB: 18972
• Descriptor: TAU-CNVA (1 entity in total)
• Functional Keywords: toxin, sst3, amidated c-terminus
• Biological source: CONUS CONSORS
• Total number of polymer chains: 1
• Total formula weight: 1724.15

Authors

Petrel, C.,Hocking, H.G.,Reynaud, M.,Favreau, P.,Paolini-Bertrand, M.,Peigneur, S.,Upert, G.,Tytgat, J.,Gilles, N.,Hartley, O.,Boelens, R.,Stocklin, R.,Servent, D. (deposition date: 2013-01-24, release date: 2013-04-24, Last modification date: 2024-11-13)

Primary citation

Petrel, C.,Hocking, H.G.,Reynaud, M.,Upert, G.,Favreau, P.,Biass, D.,Paolini-Bertrand, M.,Peigneur, S.,Tytgat, J.,Gilles, N.,Hartley, O.,Boelens, R.,Stocklin, R.,Servent, D.
Identification, Structural and Pharmacological Characterization of Tau-Cnva, a Conopeptide that Selectively Interacts with Somatostatin Sst3 Receptor.
Biochem.Pharmacol, 85:1663-, 2013

PubMed Abstract: Conopeptides are a diverse array of small linear and reticulated peptides that interact with high potency and selectivity with a large diversity of receptors and ion channels. They are used by cone snails for prey capture or defense. Recent advances in venom gland transcriptomic and venom peptidomic/proteomic technologies combined with bioactivity screening approaches lead to the identification of new toxins with original pharmacological profiles. Here, from transcriptomic/proteomic analyses of the Conus consors cone snail, we identified a new conopeptide called τ-CnVA, which displays the typical cysteine framework V of the T1-conotoxin superfamily. This peptide was chemically synthesized and its three-dimensional structure was solved by NMR analysis and compared to that of TxVA belonging to the same family, revealing very few common structural features apart a common orientation of the intercysteine loop. Because of the lack of a clear biological function associated with the T-conotoxin family, τ-CnVA was screened against more than fifty different ion channels and receptors, highlighting its capacity to interact selectively with the somatostatine sst3 receptor. Pharmacological and functional studies show that τ-CnVA displays a micromolar (Ki of 1.5μM) antagonist property for the sst3 receptor, being currently the only known toxin to interact with this GPCR subfamily.

PubMed: 23567999
DOI: 10.1016/J.BCP.2013.03.019

Experimental method

SOLUTION NMR