NDLI: Conopressin-T from Conus tulipa reveals an antagonist switch in vasopressin-like peptides.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Lumsden, Natalie G. Lewis, Richard J. Andersson, Asa Guillon, Gilles Alewood, Paul F. Muttenthaler, Markus Dutertre, Sébastien Daly, Norelle L. Craik, David J. Croker, Daniel
Description	Author Affiliation: Dutertre S ( Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland 4072, Australia.)
Abstract	We report the discovery of conopressin-T, a novel bioactive peptide isolated from Conus tulipa venom. Conopressin-T belongs to the vasopressin-like peptide family and displays high sequence homology to the mammalian hormone oxytocin (OT) and to vasotocin, the endogenous vasopressin analogue found in teleost fish, the cone snail's prey. Conopressin-T was found to act as a selective antagonist at the human V 1a receptor. All peptides in this family contain two conserved amino acids within the exocyclic tripeptide (Pro7 and Gly9), which are replaced with Leu7 and Val9 in conopressin-T. Whereas conopressin-T binds only to OT and V 1a receptors, an L7P analogue had increased affinity for the V 1a receptor and weak V2 receptor binding. Surprisingly, replacing Gly9 with Val9 in OT and vasopressin revealed that this position can function as an agonist/antagonist switch at the V 1a receptor. NMR structures of both conopressin-T and L7P analogue revealed a marked difference in the orientation of the exocyclic tripeptide that may serve as templates for the design of novel ligands with enhanced affinity for the V 1a receptor.
ISSN	00219258
e-ISSN	1083351X
Journal	Journal of Biological Chemistry
Issue Number	11
Volume Number	283
Language	English
Publisher	American Society for Biochemistry and Molecular Biology (United States)
Publisher Date	2008-03-14
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Conus Snail Metabolism Oxytocin Analogs & Derivatives Peptides Chemistry Vasopressins Animals CHO Cells Cricetinae Cricetulus Inositol Phosphates Models, Biological Receptors, Oxytocin Receptors, Vasopressin Vasotocin Research Support, Non-U.S. Gov't Biochemistry Molecular Biology
Content Type	Text
Resource Type	Article
Subject	Cell Biology Biochemistry Molecular Biology

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