Histidine‐containing host‐defence skin peptides of anurans bind Cu²⁺. An electrospray ionisation mass spectrometry and computational modelling study

Abstract

Anuran peptides which contain His, including caerin 1.8 (GLFKVLGSVAKHLLPHVVPVIAEKL-NH(2)), caerin 1.2 (GLLGVLGSVAKHVLPHVVPVIAEHL-NH(2)), Ala(15) maculatin 1.1 (GLFGVLAKVAAHVVAIEHF-NH(2)), fallaxidin 4.1 (GLLSFLPKVIGHLIHPPS-OH), riparin 5.1 (IVSYPDDAGEHAHKMG-NH(2)) and signiferin 2.1 (IIGHLIKTALGMLGL-NH(2)), all form MMet(2+) and (M + Met(2+)-2H(+))(2+) cluster ions (where Met is Cu, Mg and Zn) following electrospray ionisation (ESI) in a Waters QTOF 2 mass spectrometer. Peaks due to Cu(II) complexes are always the most abundant relative to other metal complexes. Information concerning metal(2+) connectivity in a complex has been obtained (at least in part) using b and y fragmentation data from ESI collision-induced dissociation tandem mass spectrometry (CID MS/MS). Theoretical calculations, using AMBER version 10, show that MCu(2+) complexes with the membrane active caerin 1.8, Ala(15) maculatin 1.1 and fallaxidin 4.1 are four-coordinate and approximating square planar, with ligands including His and Lys, together with the carbonyl oxygens of particular backbone amide groups. When binding can occur through two His, or one His and one Lys, the His/Lys ligand structure is the more stable for the studied systems. The three-dimensional (3D) structures of the complexes are always different from the previously determined structures of the uncomplexed model peptides (using 2D nuclear magnetic resonance (NMR) spectroscopy in membrane-mimicking solvents like trifluoroethanol/water).

Caerin 1 Antimicrobial Peptides that Inhibit HIV and Neisseria May Spare Protective Lactobacilli

“…Like, caerin 1.1, caerin 1.2, 1.9, 1.10, and 1.20 are wide-spectrum anti-bacterial agents [ 14 , 15 ]. In a membrane-like environment, they adopt a hinged amphipathic structure with two alpha-helices on either side of the hinge [ 16 , 17 , 18 ]. We included caerin 1.3 and caerin 1.4 as control peptides because they had previously been shown to have reduced antibacterial activity.…”

Mg alloy surface immobilised with caerin peptides acquires enhanced antibacterial ability and putatively improved corrosion resistance

“…However, it is very difficult to directly apply the peptides to form a stable layer outside the Mg-based alloy. Although Mg might chelate with certain side chains (e.g., His and Lys) of caerin peptides to generate a loose layer containing peptides, this layer is likely to be deformed in physiological environment and may also lead to damage on metal surface [63]. In this study we developed a coating method using click chemistry reaction to keep metal surface intact.…”

2-Dimensional HP Folding Structures of Caerin

“…。Caerin 是澳大利亚树蛙皮肤腺体中分泌的抗菌 阳离子短肽，它们通过像清洁剂一样引发跨膜小孔或者分 裂细胞膜的方式发挥作用 [3] 。通常这些包含二硫键的多肽 可以在电喷雾离子化过程中和铜、镁、锌形成复离子。关 于金属(2+)连接成一个络合物的理论计算表明 MCU(2+)与 膜活性的 Caerin 络合，如 Caerin 1.8，是 4 配位络合物且 近似正方形的平面 [4] ，因为疏水性和亲水性的相互作用对 抗菌功能都很重要 [5] ， 这激发了我们使用疏水性-极性(HP) 模型研究折叠结构，此模型依据蛋白折叠的推动力，而氨 基酸的疏水性是形成小球状蛋白天然结构的主要动力 [6] 。 任何模型都是对现实生活中案例的近似，从本质上来 讲，模型之间的不同也就体现在它们提供的相似程度不 同。HP 模型看上去很简单，却有必要进行全面研究，因 为该模型需要高强度计算，它已经被列为 NP 问题 [7] ，并 且已被列为千禧年大奖难题(Millennium Prize Problems： 七 个由美国克雷数学研究所于 2000 年 5 月 24 日公布的数学 难题)的首要问题 [8] 。因此，研究 HP 模型能够帮助我们理 解 NP 问题，开发最佳算法 [9] ，处理生物学领域的其他高 强度计算问题，例如系统发生学和核糖核酸假结问题 [10] 。 Caerin [11] ，并从通用蛋白质资源数据库中获取它们的氨基 酸序列 [12] 。从阿德里奇化学网站获取的标准化氨基酸疏水 性指数 [13] ，如表 1 所示。…”