Inhibition of yeast ribonucleotide reductase by Sml1 depends on the allosteric state of the enzyme. Issue 12 (27th May 2016)

• Record Type: Journal Article
• Authors: Misko, Tessianna A.; Wijerathna, Sanath R.; Radivoyevitch, Tomas; Berdis, Anthony J.; Ahmad, Md. Faiz; Harris, Michael E.; Dealwis, Chris G.
• Is Part Of: FEBS letters. Volume 590:Issue 12(2016)
• Page Start: 1704
• Page End: 1712
• Publication Date: 2016-05-27
• Subjects: enzyme kinetics -- intrinsically disordered protein -- mixed inhibition -- nucleotides -- oligomerization; Biochemistry -- Periodicals; Biophysics -- Periodicals; Molecular biology -- Periodicals; Biochimie -- Périodiques; Biochemistry; Biophysics; Molecular biology; Periodicals; 572.05
• DOI: 10.1002/1873-3468.12207
• Languages: English
• ISSNs: 0014-5793

Abstract

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. Abstract :