Function and structure of a prokaryotic formylglycine-generating enzyme

Brian L. Carlson, Edward R. Ballister, Emmanuel Skordalakes, David S. King, Mark A. Breidenbach, Sarah A. Gilmore, James M Berger, Carolyn R. Bertozzi

Research output: Contribution to journalArticle

Abstract

Type I sulfatases require an unusual co- or post-translational modification for their activity in hydrolyzing sulfate esters. In eukaryotic sulfatases, an active site cysteine residue is oxidized to the aldehyde-containing C α-formylglycine residue by the formylglycine-generating enzyme (FGE). The machinery responsible for sulfatase activation is poorly understood in prokaryotes. Here we describe the identification of a prokaryotic FGE from Mycobacterium tuberculosis. In addition, we solved the crystal structure of the Streptomyces coelicolor FGE homolog to 2.1 Å resolution. The prokaryotic homolog exhibits remarkable structural similarity to human FGE, including the position of catalytic cysteine residues. Both biochemical and structural data indicate the presence of an oxidized cysteine modification in the active site that may be relevant to catalysis. In addition, we generated a mutant M. tuberculosis strain lacking FGE. Although global sulfatase activity was reduced in the mutant, a significant amount of residual sulfatase activity suggests the presence of FGE-independent sulfatases in this organism.

Original languageEnglish (US)
Pages (from-to)20117-20125
Number of pages9
JournalJournal of Biological Chemistry
Volume283
Issue number29
DOIs
StatePublished - Jul 18 2008
Externally publishedYes

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Sulfatases
Enzymes
Cysteine
Mycobacterium tuberculosis
Catalytic Domain
Streptomyces coelicolor
Post Translational Protein Processing
N-formylglycine
Catalysis
Aldehydes
Sulfates
Machinery
Esters
Crystal structure
Chemical activation

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Carlson, B. L., Ballister, E. R., Skordalakes, E., King, D. S., Breidenbach, M. A., Gilmore, S. A., ... Bertozzi, C. R. (2008). Function and structure of a prokaryotic formylglycine-generating enzyme. Journal of Biological Chemistry, 283(29), 20117-20125. https://doi.org/10.1074/jbc.M800217200

Function and structure of a prokaryotic formylglycine-generating enzyme. / Carlson, Brian L.; Ballister, Edward R.; Skordalakes, Emmanuel; King, David S.; Breidenbach, Mark A.; Gilmore, Sarah A.; Berger, James M; Bertozzi, Carolyn R.

In: Journal of Biological Chemistry, Vol. 283, No. 29, 18.07.2008, p. 20117-20125.

Research output: Contribution to journalArticle

Carlson, BL, Ballister, ER, Skordalakes, E, King, DS, Breidenbach, MA, Gilmore, SA, Berger, JM & Bertozzi, CR 2008, 'Function and structure of a prokaryotic formylglycine-generating enzyme', Journal of Biological Chemistry, vol. 283, no. 29, pp. 20117-20125. https://doi.org/10.1074/jbc.M800217200
Carlson BL, Ballister ER, Skordalakes E, King DS, Breidenbach MA, Gilmore SA et al. Function and structure of a prokaryotic formylglycine-generating enzyme. Journal of Biological Chemistry. 2008 Jul 18;283(29):20117-20125. https://doi.org/10.1074/jbc.M800217200
Carlson, Brian L. ; Ballister, Edward R. ; Skordalakes, Emmanuel ; King, David S. ; Breidenbach, Mark A. ; Gilmore, Sarah A. ; Berger, James M ; Bertozzi, Carolyn R. / Function and structure of a prokaryotic formylglycine-generating enzyme. In: Journal of Biological Chemistry. 2008 ; Vol. 283, No. 29. pp. 20117-20125.
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