Calvete Juan J, Moreno-Murciano M Paz, Theakston R David G, Kisiel Dariusz G, Marcinkiewicz Cezary
Instituto de Biomedicina de Valencia, Consejo Superior de Investigaciones Cientificas, Jaime Roig 11, Spain.
Biochem J. 2003 Jun 15;372(Pt 3):725-34. doi: 10.1042/BJ20021739.
We report the isolation and amino acid sequences of six novel dimeric disintegrins from the venoms of Vipera lebetina obtusa (VLO), V. berus (VB), V. ammodytes (VA), Echis ocellatus (EO) and Echis multisquamatus (EMS). Disintegrins VLO4, VB7, VA6 and EO4 displayed the RGD motif and inhibited the adhesion of K562 cells, expressing the integrin alpha5beta1 to immobilized fibronectin. A second group of dimeric disintegrins (VLO5 and EO5) had MLD and VGD motifs in their subunits and blocked the adhesion of the alpha4beta1 integrin to vascular cell adhesion molecule 1 with high selectivity. On the other hand, disintegrin EMS11 inhibited both alpha5beta1 and alpha4beta1 integrins with almost the same degree of specificity. Comparison of the amino acid sequences of the dimeric disintegrins with those of other disintegrins by multiple-sequence alignment and phylogenetic analysis, in conjunction with current biochemical and genetic data, supports the view that the different disintegrin subfamilies evolved from a common ADAM (a disintegrin and metalloproteinase-like) scaffold and that structural diversification occurred through disulphide bond engineering.
我们报告了从钝尾蝰蛇（VLO）、极北蝰（VB）、角蝰（VA）、鼓腹咝蝰（EO）和多鳞咝蝰（EMS）毒液中分离出的六种新型二聚体去整合素的氨基酸序列。去整合素VLO4、VB7、VA6和EO4具有RGD基序，并抑制表达整合素α5β1的K562细胞与固定化纤连蛋白的黏附。第二组二聚体去整合素（VLO5和EO5）在其亚基中具有MLD和VGD基序，并以高选择性阻断α4β1整合素与血管细胞黏附分子1的黏附。另一方面，去整合素EMS11以几乎相同的特异性程度抑制α5β1和α4β1整合素。通过多序列比对和系统发育分析，将二聚体去整合素的氨基酸序列与其他去整合素的序列进行比较，并结合当前的生化和遗传数据，支持了不同去整合素亚家族从共同的ADAM（一种去整合素和金属蛋白酶样）支架进化而来，以及结构多样化通过二硫键工程发生的观点。
