The 1.8 Å crystal structure of ACTIBIND suggests a mode of action for T2 ribonucleases as antitumorigenic agents

Marina De Leeuw, Ana González, Assaf Lanir, Levava Roiz, Patricia Smirnoff, Betty Schwartz, Oded Shoseyov, Orna Almog*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

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.

Original languageAmerican English
Pages (from-to)1013-1020
Number of pages8
JournalJournal of Medicinal Chemistry
Volume55
Issue number3
DOIs
StatePublished - 9 Feb 2012

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