摘要
对以往小分子蛋白酶抑制剂及多肽毒素的研究成果作一历史性回顾,重点介绍了Bowman-Birk家族的绿豆胰蛋白酶抑制剂,对此抑制剂的Lys活性功能区作了解析.它是双头抑制剂,有两个功能区,用蛋白与基因测序、基因表达、突变、肽段合成等手段证实,其核心结构是一个由两个相连九元环组成的16肽,与天然14环肽的向日葵抑制剂极类似.另一深入研究的抑制剂是27肽的天花粉胰蛋白酶抑制剂,属于南瓜族,介绍了该家族的基因序列.多肽毒素的研究包括蝎毒毒素及芋螺毒素.本文介绍了多种东亚马氏钳蝎新的钾通道毒素,有的是钙离子依赖的BK或SK钾通道毒素,有的是电压门控毒素,有的具有两个不同的功能区,阐明了它们的构效关系.表达的重组蝎氯毒素有望用于恶性胶质瘤的治疗.芋螺毒素分子量小、序列多变、功能广泛,有更好的应用前景.从中国南海16种芋螺中纯化了50个结构新的芋螺毒素,克隆了134个新基因;确定了3个新超家族,命名为V,Y,K超家族;研究发现,在某些芋螺毒素一级结构中有新的二硫键骨架和二硫键配对、独特的模板(motif)、氨基酸的D型化等;分析了A超家族的基因组结构,在内含子的3′端有一非常保守的序列,可用作引物克隆更多新的芋螺毒素基因;阐明了个别芋螺毒素的生理功能.
This paper is a retrospect of our research works on small molecular weight protease inhibitors and peptide toxins, all of them are active peptides. The Lysin active fragment of the double headed mung bean trypsin inhibitor has been intensively studied. The approaches of sequence determination, gene expression and mutagenesis as well as peptide synthesis are used to indicate that the essen- tial core of the inhibitor is composed of two conjugated disulfide loops each with nine-residues, which shares high homology with the cyclic peptide sun flower trypsin inhibitor. Another described inhibitor is the Trichosanthes trypsin inhibitor belonging to the squish family, its gene sequence was first reported in this family. The studied peptide toxins include scorpion toxins and conotoxins. Many novel potassium channel toxins were found from the scorpion Buthus martensi Karsch, in- cluding the calcium dependent BK or SK potassium channel toxins and voltage dependent toxins. Some of them have two deferent functions displaying at separated region, their structure-function relationships were elucidated. The expressed recombinant scorpion chloride toxin has a potential in treatment of malignant gliomas. From 16 species of cone snail 50 novel conotoxin peptides were identified, and 134 novel conotoxin genes were cloned. Three unreported superfamilies were char- acterized, designated as V, Y, K superfamily, respectively; some new disulfide frame and arrangement, unique motif, D-form residue in the toxin primary structures were found; the genomic structure of A superfamily was analysed, in the intro there is a very conserved sequence at the 3＇end which could be used as a primer to clone more new conotoxin genes; the biological function of some conotoxins were elucidated.
出处
《科学通报》
EI
CAS
CSCD
北大核心
2009年第18期2734-2745,共12页
Chinese Science Bulletin
