Acta Phys. -Chim. Sin. ›› 2013, Vol. 29 ›› Issue (05): 1080-1087.doi: 10.3866/PKU.WHXB201303111

• BIOPHYSICAL CHEMISTRY • Previous Articles     Next Articles

Effects of 4-Hydroxyproline Stereochemistry on α-Conotoxin Solution Conformation

ZHANG Bing-Bing, ZHAO Cong, WANG Xue-Song, HE Lei, DU Wei-Hong   

  1. Department of Chemistry, Renmin University of China, Beijing 100872
  • Received:2013-01-08 Revised:2013-03-05 Published:2013-04-24
  • Supported by:

    The project was supported by the National Key Basic Research Program of China (973) (2011CB808503), Key Project of the Ministry of Education of China (108121), and Open Fund of State Key Laboratory of Chemical Resource Engineering of Beijing University of Chemical Technology, China (CRF-2012-C-102).


The hydroxylation of proline is a post-translational modification common in α-conotoxin and other conotoxin families. The 4-hydroxyl group of hydroxyproline adopts a trans conformation in native conotoxin, and this residue plays a key role in toxin structure and bioactivity. Little is known about the effects of the cis conformation of 4-hydroxyproline on conotoxin folding and bioactivity. The solution structures of three chemically modified α-conotoxin species containing cis- and trans-4-hydroxyproline were investigated using two-dimensional nuclear magnetic resonance (2D NMR). The selected α4/ 7-conopeptides included [γ15E]Sr1B, [O7O'/γ15E]Sr1B, and [O6O'/γ14E]Vc1A. The impact of modifying prolines cis/trans-4-hydroxyl group on the conopeptide structure was remarkable. Changing from trans- to cis-4-hydroxyproline led to notable solution conformational changes in α-conopeptide species. These included secondary structure elements, side chain orientations of key residues, and hydrogen-bonding properties. [O7O'/γ15E]Sr1B exhibited a twisted ω structure unlike that of typical α-conotoxin species. [O6O'/γ14E]Vc1A lost the turn structure around the N-/C-termini, which differed from that of Vc1.1. This study aids our understanding of the chemical modification of conotoxin, and is useful in elucidating the structure- bioactivity relationships of α-conotoxin species.

Key words: α-Conotoxin, Hydroxyproline, Stereochemistry, NMR, Solution conformation


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