De Paula V S, Silva F H S, Francischetti I M B, Monteiro R Q, Valente A P
Campus Xerém, Universidade Federal do Rio de Janeiro, Rio de Janeiro, 25245-390, Brazil.
Centro de Biologia Estrutural e Bioimagem, Rio de Janeiro, 21941-902, Brazil.
Biomol NMR Assign. 2017 Oct;11(2):293-296. doi: 10.1007/s12104-017-9766-3. Epub 2017 Aug 30.
Ixolaris is a two-Kunitz tick salivary gland protein identified in Ixodes scapularis that presents sequence homology to TFPI (tissue factor pathway inhibitor). It binds to the coagulation enzyme factor Xa (FXa) or to its zymogen form, FX, and further inhibits tissue factor/FVIIa complex (extrinsic Xnase compex). Differently from TFPI, Ixolaris does not bind to the active site cleft of FXa. Instead, complex formation is mediated by the FXa heparin-binding exosite, which may also results in decreased FXa activity into the prothrombinase complex. The Ixolaris-FXa/FX complex formation has been characterized by using a combination of biophysical and biochemical technics although no structural data is currently available. In this study, we reported the NMR chemical shift assignment of Ixolaris, as a first step to further establishing the structure, dynamics and function relationship for this protein.
艾索拉利司是在肩突硬蜱中鉴定出的一种双库尼茨蜱唾液腺蛋白，与组织因子途径抑制剂（TFPI）存在序列同源性。它与凝血酶因子Xa（FXa）或其酶原形式FX结合，并进一步抑制组织因子/FVIIa复合物（外源性Xnase复合物）。与TFPI不同，艾索拉利司不与FXa的活性位点裂隙结合。相反，复合物的形成是由FXa肝素结合外位点介导的，这也可能导致FXa在凝血酶原酶复合物中的活性降低。尽管目前尚无结构数据，但已通过结合生物物理和生化技术对艾索拉利司-FXa/FX复合物的形成进行了表征。在本研究中，我们报告了艾索拉利司的核磁共振化学位移归属，作为进一步建立该蛋白质结构、动力学和功能关系的第一步。
