2j15
From Proteopedia
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CYCLIC MRIA: AN EXCEPTIONALLY STABLE AND POTENT CYCLIC CONOTOXIN WITH A NOVEL TOPOLOGICAL FOLD THAT TARGETS THE NOREPINEPHRINE TRANSPORTER.
Overview
Conotoxins, disulfide-rich peptides from the venom of cone snails, have created much excitement over recent years due to their potency and specificity for ion channels and their therapeutic potential. One recently identified conotoxin, MrIA, a 13-residue member of the chi-conotoxin family, inhibits the human norepinephrine transporter (NET) and has potential applications in the treatment of pain. In the current study, we show that the beta-hairpin structure of native MrIA is retained in a synthetic cyclic version, as is biological activity at the NET. Furthermore, the cyclic version has increased resistance to trypsin digestion relative to the native peptide, an intriguing result because the cleavage site for the trypsin is not close to the cyclization site. The use of peptides as drugs is generally hampered by susceptibility to proteolysis, and so, the increase in enzymatic stability against trypsin observed in the current study may be useful in improving the therapeutic potential of MrIA. Furthermore, the structure reported here for cyclic MrIA represents a new topology among a growing number of circular disulfide-rich peptides.
About this Structure
2J15 is a Single protein structure of sequence from [1]. Full crystallographic information is available from OCA.
Reference
Cyclic MrIA: a stable and potent cyclic conotoxin with a novel topological fold that targets the norepinephrine transporter., Lovelace ES, Armishaw CJ, Colgrave ML, Wahlstrom ME, Alewood PF, Daly NL, Craik DJ, J Med Chem. 2006 Nov 2;49(22):6561-8. PMID:17064074
Page seeded by OCA on Mon Mar 31 03:51:41 2008
