Department of Clinical Biochemistry, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva 84105, Israel.
J Med Chem. 2012 Feb 9;55(3):1013-20. doi: 10.1021/jm1015507. Epub 2012 Jan 31.
ACTIBIND and its human homologue RNASET2 are T2 ribonucleases (RNases). RNases are ubiquitous and efficient enzymes that hydrolyze RNA to 3' mononucleotides and also possess antitumorigenic and antiangiogenic activities. Previously, we have shown that ACTIBIND and RNASET2 bind actin and interfere with the cytoskeletal network structure, thereby inhibiting cell motility and invasiveness in cancer and in endothelial cells. We also showed that ACTIBIND binds actin in a molar ratio of 1:2. Here, we further characterize ACTIBIND and determine its crystal structure at 1.8 Å resolution, which enables us to propose two structural elements that create binding sites to actin. We suggest that each of these binding sites is composed of one cysteine residue and one conserved amino acid region. These binding sites possibly interfere with the cytoskeleton network structure and as such may be responsible for the antitumorigenic and antiangiogenic activities of ACTIBIND and its human analogue RNASET2.
ACTIBIND 及其同源物 RNASET2 是 T2 核糖核酸酶 (RNases)。RNases 是普遍存在且高效的酶，能够将 RNA 水解为 3' 单核苷酸，同时还具有抗肿瘤和抗血管生成活性。此前，我们已经表明 ACTIBIND 和 RNASET2 结合肌动蛋白并干扰细胞骨架网络结构，从而抑制癌症和内皮细胞的运动性和侵袭性。我们还表明 ACTIBIND 以 1:2 的摩尔比结合肌动蛋白。在这里，我们进一步表征了 ACTIBIND，并确定了其在 1.8Å 分辨率下的晶体结构，这使我们能够提出两个创建与肌动蛋白结合位点的结构元素。我们假设这些结合位点中的每一个都由一个半胱氨酸残基和一个保守的氨基酸区域组成。这些结合位点可能会干扰细胞骨架网络结构，因此可能是 ACTIBIND 和其人类类似物 RNASET2 的抗肿瘤和抗血管生成活性的原因。
