2jqc: Difference between revisions

[[Image:2jqc.jpg|left|200px]]

'''A L-amino acid mutant of a D-amino acid containing conopeptide'''

Cone snails, a group of gastropod animals that inhabit tropical seas, are capable of producing a mixture of peptide neurotoxins, namely conotoxins, for defense and predation. Conotoxins are mainly disulfide-rich short peptides that act on different ion channels, neurotransmitter receptors, or transporters in the nervous system. They exhibit highly diverse compositions, structures, and biological functions. In this work, a novel Cys-free 15-residue conopeptide from Conus marmoreus was purified and designated as conomarphin. Conomarphin is unique because of its d-configuration Phe at the third residue from the C-terminus, which was identified using HPLC by comparing native conomarphin fragments and the corresponding synthetic peptides cleaved by different proteases. Surprisingly, the cDNA-encoded precursor of conomarphin was found to share the conserved signal peptide with other M-superfamily conotoxins, clearly indicating that conomarphin should belong to the M-superfamily, although conomarphin shares no homology with other six-Cys-containing M-superfamily conotoxins. Furthermore, NMR spectroscopy experiments established that conomarphin adopts a well-defined structure in solution, with a tight loop in the middle of the peptide and a short 3(10)-helix at the C-terminus. By contrast, no loop in l-Phe13-conomarphin was found, which suggests that d-Phe13 is essential for the structure of conomarphin. In conclusion, conomarphin may represent a new conotoxin family, whose biological activity remains to be identified.

Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2JQC OCA].  

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