物理化学学报Issue(5)：1080-1087,8.DOI:10.3866/PKU.WHXB201303111
4-羟基脯氨酸立体异构对α-芋螺毒素溶液构象的影响
Effects of 4-Hydroxyproline Stereochemistry onα-Conotoxin Solution Conformation
摘要
Abstract
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 chemical y 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, [O7Oʹ/γ15E]Sr1B, and [O6Oʹ/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. [O7Oʹ/γ15E]Sr1B exhibited a twisted ω structure unlike that of typical α-conotoxin species. [O6Oʹ/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 ofα-conotoxin species.关键词
α-芋螺毒素/羟脯氨酸/立体异构/核磁共振/溶液构象Key words
α-Conotoxin/Hydroxyproline/Stereochemistry/NMR/Solution conformation分类
化学化工引用本文复制引用
张兵兵,赵聪,王雪松,何蕾,杜为红..4-羟基脯氨酸立体异构对α-芋螺毒素溶液构象的影响[J].物理化学学报,2013,(5):1080-1087,8.基金项目
国家重点基础研究发展规划项目(973)(2011CB808503),教育部科技重点项目(108121)及北京化工大学化工资源有效利用国家重点实验室开放课题(CRF-2012-C-102)资助.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) （973）
