6ppc

Publication Abstract from PubMed

Conotoxins are a large family of disulfide-rich peptides that contain unique cysteine frameworks that target a broad range of ion channels and receptors. We recently discovered the 33-residue conotoxin Phi-MiXXVIIA from Conus miles with a novel cysteine framework comprising three consecutive cysteine residues and four disulfide bonds. Regioselective chemical synthesis helped decipher the disulfide bond connectivity and the structure of Phi-MiXXVIIA was determined by NMR spectroscopy. The 3D structure displays a unique topology containing two beta-hairpins that resemble the N-terminal domain of granulin. Similar to granulin, Phi-MiXXVIIA promotes cell proliferation (EC50 17.85 mum) while inhibiting apoptosis (EC50 2.2 mum). Additional framework XXVII sequences were discovered with homologous signal peptides that define the new conotoxin superfamily G2. The novel structure and biological activity of Phi-MiXXVIIA expands the repertoire of disulfide-rich conotoxins that recognize mammalian receptors.

Conotoxin Phi-MiXXVIIA from the Superfamily G2 Employs a Novel Cysteine Framework that Mimics Granulin and Displays Anti-Apoptotic Activity.,Jin AH, Dekan Z, Smout MJ, Wilson D, Dutertre S, Vetter I, Lewis RJ, Loukas A, Daly NL, Alewood PF Angew Chem Int Ed Engl. 2017 Nov 20;56(47):14973-14976. doi:, 10.1002/anie.201708927. Epub 2017 Oct 24. PMID:28984021^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.