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Inhibition of yeast ribonucleotide reductase by Sml1 depends on the allosteric state of the enzyme
Author(s) -
Misko Tessianna A.,
Wijerathna Sanath R.,
Radivoyevitch Tomas,
Berdis Anthony J.,
Ahmad Md. Faiz,
Harris Michael E.,
Dealwis Chris G.
Publication year - 2016
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.12207
Subject(s) - ribonucleotide reductase , allosteric regulation , saccharomyces cerevisiae , biochemistry , enzyme , nucleotide , chemistry , mutagenesis , yeast , ribonucleotide , biology , mutation , protein subunit , gene
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.