CAJ | 학술논문

在α-芋螺毒素及其它家族的芋螺毒素中,脯氨酸的羟基化是非常普遍的后转录修饰方式.在天然芋螺毒素中脯氨酸的羟基常采用反式构型,且该残基对芋螺毒素的结构与生物活性产生了重要的影响,而顺式构型的羟脯氨酸对α-芋螺毒素的折叠与生物活性的影响还鲜有研究.本工作通过二维(2D)溶液核磁共振方法测定了经过化学修饰的三个含有反式或顺式羟脯氨酸的α-芋螺毒素的溶液结构,它们是α4/7亚家族芋螺毒素肽[γ15E]Sr1B、[O7O?/γ15E]Sr1B和[O6O?/γ14E]Vc1A.研究表明,羟基顺反异构化学修饰对芋螺毒素的结构影响显著.羟脯氨酸羟基的反式到顺式修饰导致α-芋螺毒素肽明显的溶液构象变化,这些变化包括二级结构的改变、关键残基的侧链取向变化以及氢键性质的改变.[O7O?/γ15E]Sr1B与[γ15E]Sr1B相比,典型的α-芋螺毒素ω弯曲结构发生形变.而[O6O?/γ14E]Vc1A不同于Vc1A的是末端转角结构的缺失.本工作加深了对α-芋螺毒素肽的化学修饰法的理解,该方法是阐明α-芋螺毒素结构-生物活性关系的有用工具.
재α-우라독소급기타가족적우라독소중,포안산적간기화시비상보편적후전록수식방식.재천연우라독소중포안산적간기상채용반식구형,차해잔기대우라독소적결구여생물활성산생료중요적영향,이순식구형적간포안산대α-우라독소적절첩여생물활성적영향환선유연구.본공작통과이유(2D)용액핵자공진방법측정료경과화학수식적삼개함유반식혹순식간포안산적α-우라독소적용액결구,타문시α4/7아가족우라독소태[γ15E]Sr1B、[O7O?/γ15E]Sr1B화[O6O?/γ14E]Vc1A.연구표명,간기순반이구화학수식대우라독소적결구영향현저.간포안산간기적반식도순식수식도치α-우라독소태명현적용액구상변화,저사변화포괄이급결구적개변、관건잔기적측련취향변화이급경건성질적개변.[O7O?/γ15E]Sr1B여[γ15E]Sr1B상비,전형적α-우라독소ω만곡결구발생형변.이[O6O?/γ14E]Vc1A불동우Vc1A적시말단전각결구적결실.본공작가심료대α-우라독소태적화학수식법적리해,해방법시천명α-우라독소결구-생물활성관계적유용공구.
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, [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 ofα-conotoxin species.