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Mechanism of Type IA Topoisomerases

Department of Chemistry and Biochemistry, Florida International University, Miami, FL 33199, USA
Biomolecular Sciences Institute, Florida International University, Miami, FL 33199, USA
Biochemistry PhD Program, Florida International University, Miami, FL 33199, USA
Author to whom correspondence should be addressed.
Academic Editor: Dagmar Klostermeier
Molecules 2020, 25(20), 4769;
Received: 21 September 2020 / Revised: 12 October 2020 / Accepted: 15 October 2020 / Published: 17 October 2020
Topoisomerases in the type IA subfamily can catalyze change in topology for both DNA and RNA substrates. A type IA topoisomerase may have been present in a last universal common ancestor (LUCA) with an RNA genome. Type IA topoisomerases have since evolved to catalyze the resolution of topological barriers encountered by genomes that require the passing of nucleic acid strand(s) through a break on a single DNA or RNA strand. Here, based on available structural and biochemical data, we discuss how a type IA topoisomerase may recognize and bind single-stranded DNA or RNA to initiate its required catalytic function. Active site residues assist in the nucleophilic attack of a phosphodiester bond between two nucleotides to form a covalent intermediate with a 5′-phosphotyrosine linkage to the cleaved nucleic acid. A divalent ion interaction helps to position the 3′-hydroxyl group at the precise location required for the cleaved phosphodiester bond to be rejoined following the passage of another nucleic acid strand through the break. In addition to type IA topoisomerase structures observed by X-ray crystallography, we now have evidence from biophysical studies for the dynamic conformations that are required for type IA topoisomerases to catalyze the change in the topology of the nucleic acid substrates. View Full-Text
Keywords: topoisomerase; type IA; DNA supercoiling; RNA topology; decatenation topoisomerase; type IA; DNA supercoiling; RNA topology; decatenation
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MDPI and ACS Style

Dasgupta, T.; Ferdous, S.; Tse-Dinh, Y.-C. Mechanism of Type IA Topoisomerases. Molecules 2020, 25, 4769.

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