Snake venom disintegrins: novel dimeric disintegrins and structural diversification by disulphide bond engineering
Snake venom disintegrins: novel dimeric disintegrins and structural diversification by disulphide bond engineering
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DOI：
10.1042/bj20021739
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发表时间：
2003-06-15
影响因子：
4.1
通讯作者：
Marcinkiewicz, C
中科院分区：
文献类型：
--
作者：
Calvete, JJ;Moreno-Murciano, MP;Marcinkiewicz, C
本文报道了从长尾蝮蛇（Vipera lebetina obtusa， VLO）、V berus （VB）、V ammodytes （VA）、Echis ocellatus （EO）和Echis multisquamatus （EMS）毒液中分离得到的6种新型二聚体崩解素及其氨基酸序列。Disintegrins, VLO4, VB7， VA6和EO4显示RGD基序，抑制K562细胞的粘附，表达整合素alpha5beta1到固定化纤维连接蛋白。第二组二聚体崩解素（VLO5和EO5）在其亚基中具有MLD和VGD基序，并以高选择性阻断α 4beta1整合素与血管细胞粘附分子1的粘附。另一方面，崩解素EMS11抑制alpha5beta1和alpha4beta1整合素的特异性几乎相同。将二聚体崩解素与其他崩解素的氨基酸序列进行多序列对比和系统发育分析，结合现有的生化和遗传数据，支持了不同崩解素亚家族从一个共同的ADAM（崩解素和金属蛋白酶样）支架进化而来的观点，结构多样化是通过二硫键工程发生的。
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.