Structure of Sir2Tm bound to a propionylated peptide

Poonam Bheda, Jennifer T. Wang, Jorge C. Escalante-Semerena, Cynthia Wolberger

Research output: Contribution to journalArticle

Abstract

Lysine propionylation is a recently identified post-translational modification that has been observed in proteins such as p53 and histones and is thought to play a role similar to acetylation in modulating protein activity. Members of the sirtuin family of deacetylases have been shown to have depropionylation activity, although the way in which the sirtuin catalytic site accommodates the bulkier propionyl group is not clear. We have determined the 1.8 Å structure of a Thermotoga maritima sirtuin, Sir2Tm, bound to a propionylated peptide derived from p53. A comparison with the structure of Sir2Tm bound to an acetylated peptide shows that hydrophobic residues in the active site shift to accommodate the bulkier propionyl group. Isothermal titration calorimetry data show that Sir2Tm binds propionylated substrates more tightly than acetylated substrates, but kinetic assays reveal that the catalytic rate of Sir2Tm deacylation of propionyllysine is slightly reduced to acetyl-lysine. These results serve to broaden our understanding of the newly identified propionyl-lysine modification and the ability of sirtuins to depropionylate, as well as deacetylate, substrates.

Original languageEnglish (US)
Pages (from-to)131-139
Number of pages9
JournalProtein Science
Volume20
Issue number1
DOIs
StatePublished - Jan 2011

Fingerprint

Lysine
Peptides
Catalytic Domain
Substrates
Sirtuins
Thermotoga maritima
Acetylation
Calorimetry
Aptitude
Post Translational Protein Processing
Titration
Histones
Assays
Proteins
Kinetics

Keywords

  • Deacetylation
  • Depropionylation
  • Propionyl-lysine
  • Sir2
  • Sirtuin
  • T. maritima

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

Cite this

Bheda, P., Wang, J. T., Escalante-Semerena, J. C., & Wolberger, C. (2011). Structure of Sir2Tm bound to a propionylated peptide. Protein Science, 20(1), 131-139. https://doi.org/10.1002/pro.544

Structure of Sir2Tm bound to a propionylated peptide. / Bheda, Poonam; Wang, Jennifer T.; Escalante-Semerena, Jorge C.; Wolberger, Cynthia.

In: Protein Science, Vol. 20, No. 1, 01.2011, p. 131-139.

Research output: Contribution to journalArticle

Bheda, P, Wang, JT, Escalante-Semerena, JC & Wolberger, C 2011, 'Structure of Sir2Tm bound to a propionylated peptide', Protein Science, vol. 20, no. 1, pp. 131-139. https://doi.org/10.1002/pro.544
Bheda, Poonam ; Wang, Jennifer T. ; Escalante-Semerena, Jorge C. ; Wolberger, Cynthia. / Structure of Sir2Tm bound to a propionylated peptide. In: Protein Science. 2011 ; Vol. 20, No. 1. pp. 131-139.
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