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Inhibition of yeast ribonucleotide reductase by Sml1 depends on the allosteric state of the enzyme.

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.

SUBMITTER: Misko TA

PROVIDER: S-EPMC4925217 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature

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Inhibition of yeast ribonucleotide reductase by Sml1 depends on the allosteric state of the enzyme.

Misko Tessianna A TA Wijerathna Sanath R SR Radivoyevitch Tomas T Berdis Anthony J AJ Ahmad Md Faiz MF Harris Michael E ME Dealwis Chris G CG

FEBS letters 20160527 12

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 weak ...[more]

PMID: 27155231

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