The crystal structure of human cathepsin F and its implications for the development of novel immunomodulators

被引：50

作者：

Somoza, JR ^{[1
]}

Palmer, JT ^{[1
]}

Ho, JD ^{[1
]}

机构：

[1] Dept Med & Struct Chem, San Francisco, CA 94080 USA

来源：

JOURNAL OF MOLECULAR BIOLOGY | 2002年 / 322卷 / 03期

基金：

美国国家卫生研究院;

关键词：

drug design; proteinase; papain family; cysteine protease; vinyl sulfone;

D O I：

10.1016/S0022-2836(02)00780-5

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Cathepsin F is a lysosomal cysteine protease of the papain family, and likely plays a regulatory role in processing the invariant chain that is associated with the major histocompatibility complex (MHC) class II. Evidence suggests that inhibiting cathepsin F activity will block MHC class II processing in macrophages. Consequently, inhibitors of this enzyme may be useful in treating certain diseases that involve an inappropriate or excessive immune response. We have determined the 1.7 A structure of the mature domain of human cathepsin F associated with an irreversible vinyl sulfone inhibitor. This structure provides a basis for understanding cathepsin F's substrate specificity, and suggests ways of identifying potent and selective inhibitors of this enzyme. (C) 2002 Elsevier Science Ltd. All rights reserved.

引用

收藏

页码：559 / 568

页数：10

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