Inhibition of Yeast Ribonucleotide Reductase by Sml1 Depends on the Allosteric State of the Enzyme

Overview

Journal FEBS Lett

Specialty Biochemistry

Date 2016 May 8

PMID 27155231

Citations 3

Authors

Tessianna A Misko

Sanath R Wijerathna

Tomas Radivoyevitch

Anthony J Berdis

Md Faiz Ahmad

Michael E Harris

Chris G Dealwis

Affiliations

Soon will be listed here.

Abstract

Sml1 is an intrinsically disordered protein inhibitor of Saccharomyces cerevisiae ribonucleotide reductase (ScRR1), but its inhibition mechanism is poorly understood. RR reduces ribonucleoside diphosphates to their deoxy forms, and balances the nucleotide pool. Multiple turnover kinetics show that Sml1 inhibition of dGTP/ADP- and ATP/CDP-bound ScRR follows a mixed inhibition mechanism. However, Sml1 cooperatively binds to the ES complex in the dGTP/ADP form, whereas with ATP/CDP, Sml1 binds weakly and noncooperatively. Gel filtration and mutagenesis studies indicate that Sml1 does not alter the oligomerization equilibrium and the CXXC motif is not involved in the inhibition. The data suggest that Sml1 is an allosteric inhibitor.

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