The 1.8 脜 Crystal Structure of ACTIBIND Suggests a Mode of Action for T2 Ribonucleases As Antitumorigenic Agents

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• 作者：Marina de Leeuw ; Ana Gonz谩lez ; Assaf Lanir ; Levava Roiz ; Patricia Smirnoff ; Betty Schwartz ; Oded Shoseyov ; Orna Almog
• 刊名：Journal of Medicinal Chemistry
• 出版年：2012
• 出版时间：February 9, 2012
• 年：2012
• 卷：55
• 期：3
• 页码：1013-1020
• 全文大小：579K
• 年卷期：v.55,no.3(February 9, 2012)
• ISSN：1520-4804

文摘

ACTIBIND and its human homologue RNASET2 are T2 ribonucleases (RNases). RNases are ubiquitous and efficient enzymes that hydrolyze RNA to 3鈥?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 脜 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.