Kazal型蛋白酶抑制剂结构与功能研究进展  

Progresses in the Structure and Function of Kazal-type Proteinase Inhibitors

作　　者：郑青亮[1] 盛清[1] 张耀洲[1] 

机构地区：[1]浙江理工大学生命科学学院生物化学研究所,杭州310018

出　　处：《生物工程学报》2006年第5期695-700,共6页Chinese Journal of Biotechnology

基　　金：国家高技术研究与发展计划项目(No.2005AA206120和No.2005BA711A07);国家973项目(No.2005CB121006);浙江省自然科学基金重点项目(No.Z204267)资助.~~

摘　　要：蛋白酶抑制剂广泛存在于生物体内,在许多生命活动过程中发挥必不可少的作用,特别是对蛋白酶活性进行精确调控。其中Kazal型蛋白酶抑制剂是最重要的、研究最为广泛的酶抑制剂之一,该类抑制剂一般由一个或几个结构域组成,每一个结构域具有保守的序列和分子构象,同时发现该类抑制剂与蛋白酶作用的结合部位高度易变,它们大多数暴露于与溶剂接触的环上,其中P1部位是抑制作用的关键部位,抑制剂的专一性由P1部位氨基酸残基的性质决定,其它残基取代结合部位残基对抑制剂-酶的结合常数有显著的影响。Laskowski算法可直接从Kazal型丝氨酸蛋白酶抑制剂的序列推测其与6种丝氨酸蛋白酶之间的抑制常数(Ki)。目前在生物体内发现大量的Kazal型蛋白酶抑制剂,并证实其有重要的生物学功能。Proteinase inhibitors are widely distributed in many living organisms and play crucial roles in many biological processes, particularly in regulating the proteinase activity spatially and temporally. However,The Kazal family of serine protease inhibitors is one of the most important and extensively studied protease inhibitor families. This type of protease inhibitor normally consists of one or several domains. Every domain has a highly conserved sequence structure and molecular conformation. It is found that contact residues are hyper variable, which are responsible for the interaction of inhibitors and proteinases. Most of them are in the solvent exposed loop. But P1 residue is the key active site of the interaction between inhibitor and enzyme.The types of the amino acid at P1 site likely play an important role in causing different inhibitory activity. The substitutions at the contact residues cause significant effects on the association constant. By using the Laskowski algorithm, the Ki values of a Kazal domain against six serine proteinases can be predicted from the domain＇ s sequence alone. At present there are many Kazal proteinase inhibitors found in the organisms, which show important biological functions. This article gives a comprehensive review of the newer developments in the characters and the interaction of the Kazal-type inhibitors.

关 键 词：Kazal型蛋白酶抑制剂 Laskowski算法 活性部位 

分 类 号：Q51[生物学—生物化学]