期刊
BIOCHIMIE
卷 166, 期 -, 页码 52-76出版社
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.biochi.2019.09.004
关键词
Allosteric network; Chymotrypsin fold; Regulatory mechanism; Structure-function relationship; Surface loops; Zymogenicity
资金
- Institute of Health and Biomedical Innovation (IHBI) at the Queensland University of Technology in Brisbane (Australia)
- Wilhelm Sander-Stiftung [2016-024.1]
- Deutsche Forschungsgemeinschaft [MA 1236/10-1]
- [I3877]
Trypsin and chymotrypsin-like serine proteases from family S1 (clan PA) constitute the largest protease group in humans and more generally in vertebrates. The prototypes chymotrypsin, trypsin and elastase represent simple digestive proteases in the gut, where they cleave nearly any protein. Multidomain trypsin-like proteases are key players in the tightly controlled blood coagulation and complement systems, as well as related proteases that are secreted from diverse immune cells. Some serine proteases are expressed in nearly all tissues and fluids of the human body, such as the human kallikreins and kallikrein-related peptidases with specialization for often unique substrates and accurate timing of activity. HtrA and membrane-anchored serine proteases fulfill important physiological tasks with emerging roles in cancer. The high diversity of all family members, which share the tandem 0-barrel architecture of the chymotrypsin-fold in the catalytic domain, is conferred by the large differences of eight surface loops, surrounding the active site. The length of these loops alters with insertions and deletions, resulting in remarkably different three-dimensional arrangements. In addition, metal binding sites for Na+, Ca2+ and Zn2+ serve as regulatory elements, as do N-glycosylation sites. Depending on the individual tasks of the protease, the surface loops determine substrate specificity, control the turnover and allow regulation of activation, activity and degradation by other proteins, which are often serine proteases themselves. Most intriguingly, in some serine proteases, the surface loops interact as allosteric network, partially tuned by protein co-factors. Knowledge of these subtle and complicated molecular motions may allow nowadays for new and specific pharmaceutical or medical approaches. (C) 2019 Elsevier B.V. and Societe Francaise de Biochimie et Biologie Moleculaire (SFBBM). All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据