Temple University, College of Science and Technology, Department of Biology, Philadelphia, PA 19122, United States.
Toxicon. 2011 Sep 15;58(4):355-62. doi: 10.1016/j.toxicon.2011.07.004. Epub 2011 Jul 21.
Snake venom disintegrins are present in a variety of species and are functionally divided into three families: RGD, MLD and R/KTS. The RGD family of disintegrins, which bind and inhibit the physiological functions of RGD-dependent integrins, constitute the largest and most investigated family. This review will be focused on characterization of two relatively new families of snake venom disintegrins, expressing in their active site MLD and R/KTS motifs. The MLD motif, present only in heterodimeric disintegrins, mediates binding of these disintegrins to α4β1, α4β7 and α9β1 integrins, whereas the presence of a KTS or RTS sequence in the active site selectively directs activity of disintegrins to the collagen receptor α1β1 integrin. Structurally, KTS-disintegrins are short, monomeric molecules containing 41 amino acids in its polypeptide chain. Biological activities of MLD and KTS-disintegrins were investigated in many systems in vitro and in vivo. Purified disintegrins are non-toxic in therapeutic doses in rodent and avian models. Their modulatory properties were observed in investigations of cancer angiogenesis and metastasis, immunosuppression of IDDM (insulin-dependent diabetes mellitus) and asthma, as well as in neurodegenerative assays and cell apoptosis.
蛇毒金属蛋白酶是存在于多种物种中的一种功能蛋白，可分为 3 个家族：RGD、MLD 和 R/KTS。RGD 家族的金属蛋白酶通过结合并抑制依赖 RGD 的整合素的生理功能，是目前研究最多的家族。本综述将重点介绍两种相对较新的蛇毒金属蛋白酶家族，它们在其活性位点表达 MLD 和 R/KTS 基序。MLD 基序仅存在于异二聚体金属蛋白酶中，介导这些金属蛋白酶与α4β1、α4β7 和α9β1 整合素的结合，而活性位点中存在 KTS 或 RTS 序列则选择性地将金属蛋白酶的活性导向胶原受体α1β1 整合素。结构上，KTS 金属蛋白酶是一种短的单体分子，其多肽链中含有 41 个氨基酸。MLD 和 KTS 金属蛋白酶在许多体外和体内系统中进行了生物活性研究。在啮齿动物和禽类模型中，在治疗剂量下，纯化的金属蛋白酶没有毒性。在癌症血管生成和转移、IDDM（胰岛素依赖型糖尿病）和哮喘的免疫抑制、神经退行性疾病检测和细胞凋亡的研究中观察到了它们的调节特性。
