锌金属蛋白酶家族介绍及结构机理研究进展

锌金属蛋白酶是一类分布广泛，种类繁多的水解酶家族，是近年来人们研究的热点．一般来说，HEXXH保守序列一直都作为锌金属蛋白酶家族分类的依据．除此之外，不同种类的酶还有一些其它的序列特征．谷氨酸锌蛋白（gluzincin）在锌离子配体处共有2组保守区域；甲硫氨酸锌蛋白（metzincin）则拥有1个延长的保守序列HEBXHXBGBXH，里面包含了第3个His配体．大量的金属蛋白酶晶体结构被解析出来，从中可以发现该类酶的活性中心都包含有1个锌离子．锌金属蛋白酶的催化机理通常认为是锌离子与1个水分子结合活化而成．但是,最近的发现证实了并不是所有的锌金属蛋白酶催化都需要水分子参与活化．在本文中，综述了这些已发表的锌金属蛋白酶家族的分类、结构特征、底物特异性识别和催化机理．

Structure Analysis of Zinc Metalloproteases

In recent years, the number of identified zinc metalloproteases of distinct families and sequences has rapidly increased with the common HEXXH motif. Gluzincins have two well-conserved regions for zinc binding. The metzincins have a long consensus sequence of HEBXHXBGBXH interacting with three of the zinc atoms. The crystal structures of a number of zinc metalloproteases have been resolved, all of which are endoproteases harboring one Zn2+ at the active centers. The catalytic mechanism of zinc metalloproteases is a typical base-catalysis reaction that involves the Zn ion and a putative water molecule. Interestingly, It was also reported that water might not bind the Zn-ion during the transition state for certain zinc metalloproteases. In this review, the classification, structural characteristics, substrate specificity, and catalytic mechanisms of zinc metalloproteases are discussed.