Kini R Manjunatha
Protein Science Laboratory, Department of Biological Sciences, Faculty of Science, National University of Singapore, 14 Science Drive 4, Singapore.
Biochem J. 2006 Aug 1;397(3):377-87. doi: 10.1042/BJ20060302.
Over the last several decades, research on snake venom toxins has provided not only new tools to decipher molecular details of various physiological processes, but also inspiration to design and develop a number of therapeutic agents. Blood circulation, particularly thrombosis and haemostasis, is one of the major targets of several snake venom proteins. Among them, anticoagulant proteins have contributed to our understanding of molecular mechanisms of blood coagulation and have provided potential new leads for the development of drugs to treat or to prevent unwanted clot formation. Some of these anticoagulants exhibit various enzymatic activities whereas others do not. They interfere in normal blood coagulation by different mechanisms. Although significant progress has been made in understanding the structure-function relationships and the mechanisms of some of these anticoagulants, there are still a number of questions to be answered as more new anticoagulants are being discovered. Such studies contribute to our fight against unwanted clot formation, which leads to death and debilitation in cardiac arrest and stroke in patients with cardiovascular and cerebrovascular diseases, arteriosclerosis and hypertension. This review describes the details of the structure, mechanism and structure-function relationships of anticoagulant proteins from snake venoms.
在过去几十年里,对蛇毒毒素的研究不仅为解读各种生理过程的分子细节提供了新工具,也为设计和开发多种治疗药物带来了灵感。血液循环,尤其是血栓形成和止血,是多种蛇毒蛋白的主要作用靶点之一。其中,抗凝蛋白有助于我们理解血液凝固的分子机制,并为开发治疗或预防不必要血栓形成的药物提供了潜在的新线索。这些抗凝蛋白中有些具有多种酶活性,而有些则没有。它们通过不同机制干扰正常的血液凝固。尽管在理解其中一些抗凝蛋白的结构-功能关系和作用机制方面已经取得了重大进展,但随着更多新型抗凝蛋白的发现,仍有许多问题有待解答。此类研究有助于我们对抗不必要的血栓形成,血栓形成会导致患有心血管和脑血管疾病、动脉硬化和高血压的患者在心脏骤停和中风时死亡和虚弱。本文综述了蛇毒抗凝蛋白的结构、作用机制以及结构-功能关系的详细情况。