Structure-based design and protein engineering of intersubunit disulfide bonds in gonadotropins

被引：40

作者：

Heikoop, JC ^{[1
]}

vandenBoogaart, P ^{[1
]}

Mulders, JWM ^{[1
]}

Grootenhuis, PDJ ^{[1
]}

机构：

[1] NV ORGANON, NL-5340 BH OSS, NETHERLANDS

来源：

NATURE BIOTECHNOLOGY | 1997年 / 15卷 / 07期

关键词：

protein engineering; rational design; molecular modeling; human choriogonadotropin; luteinizing hormone; follicle stimulating hormone;

D O I：

10.1038/nbt0797-658

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

Pairs of cystine residues were introduced in the alpha- and beta-subunits of human choriogonadotropin at positions with optimal geometries for the formation of disulfide bonds. Using the homology with luteinizing hormone and follicle stimulating hormone, similar mutations were carried out in these glycoprotein hormones. In nearly all mutants the corresponding disulfide bonds were formed leading to a non-natural, covalent linkage between the alpha- and beta-subunits. The mutants typically display wild-type receptor binding and bioactivity. The mutants with non-natural intersubunit disulfide bonds display enhanced thermostabilities relative to the corresponding heterodimeric glycoprotein hormones, rendering them candidates for long acting gonadotropins with enhanced shelf lives.

引用

页码：658 / 662

页数：5

共 29 条

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