Biochemistry Research Group, Department of Biological Sciences, University of Calgary, Calgary, Alberta, Canada.
Sci Rep. 2016 Aug 24;6:31817. doi: 10.1038/srep31817.
Staphylokinase (Sak) is a plasminogen activator protein that is secreted by many Staphylococcus aureus strains. Sak also offers protection by binding and inhibiting specific antimicrobial peptides (AMPs). Here, we evaluate Sak as a more general interaction partner for AMPs. Studies with melittin, mCRAMP, tritrpticin and bovine lactoferricin indicate that the truncation of the first ten residues of Sak (SakΔN10), which occurs in vivo and uncovers important residues in a bulge region, improves its affinity for AMPs. Melittin and mCRAMP have a lower affinity for SakΔN10, and in docking studies, they bind to the N-terminal segment and bulge region of SakΔN10. By comparison, lactoferricin and tritrpticin form moderately high affinity 1:1 complexes with SakΔN10 and their cationic residues form several electrostatic interactions with the protein's α-helix. Overall, our work identifies two distinct AMP binding surfaces on SakΔN10 whose occupation would lead to either inhibition or promotion of its plasminogen activating properties.
葡萄球菌激酶（Sak）是一种纤溶酶原激活蛋白，许多金黄色葡萄球菌菌株都会分泌这种蛋白。Sak 还可以通过与特定的抗菌肽（AMPs）结合并抑制这些抗菌肽来提供保护。在这里，我们将 Sak 评估为 AMPs 的更通用的相互作用伙伴。用蜂毒素、mCRAMP、三肽菌素和牛乳铁蛋白进行的研究表明，Sak 中前 10 个残基的截断（SakΔN10）会在体内发生，暴露出隆起区域中的重要残基，从而提高其与 AMPs 的亲和力。蜂毒素和 mCRAMP 与 SakΔN10 的亲和力较低，在对接研究中，它们结合到 SakΔN10 的 N 端片段和隆起区域。相比之下，乳铁蛋白和三肽菌素与 SakΔN10 形成中等亲和力的 1:1 复合物，其阳离子残基与蛋白质的α-螺旋形成几个静电相互作用。总的来说，我们的工作确定了 SakΔN10 上两个不同的 AMP 结合表面，占据这些表面将导致抑制或促进其纤溶酶原激活特性。
