Catalytic phosphoryl interactions of topoisomerase IB

Rajesh Nagarajan, Keehwan Kwon, Barbara Nawrot, Wojciech J. Stec, James T. Stivers

Research output: Contribution to journalArticlepeer-review

Abstract

The reversible nucleophilic substitution reaction catalyzed by the vaccinia virus type IB topoisomerase has been investigated by measuring the equilibrium and rate effects of stereospecific sulfur substitution at the two nonbridging oxygen atoms of the attacked phosphodiester group. An energetic analysis of the combined effects of sulfur substitution and site-directed mutagenesis of active site residues of the enzyme has identified enzyme interactions with each oxygen in the ground state and transition state. We use these findings in combination with previous structural and 5′-bridging sulfur substitution results to deduce the web of enzymatic interactions with the nonbridging oxygens as well as the 5′-hydroxyl leaving group. A key finding is the central role of Arg130, which forms electrostatic interactions with both nonbridging oxygens and the 5′-leaving group.

Original languageEnglish (US)
Pages (from-to)11476-11485
Number of pages10
JournalBiochemistry
Volume44
Issue number34
DOIs
StatePublished - Aug 30 2005

ASJC Scopus subject areas

  • Biochemistry

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