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J. Biol. Chem., Vol. 283, Issue 29, 20117-20125, July 18, 2008

This Article Free via Author's Choice: AC AC Full Text Full Text (PDF) Supplemental Data AC All Versions of this Article: 283/29/20117    most recent M800217200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Carlson, B. L. Articles by Bertozzi, C. R. PubMed PubMed Citation Articles by Carlson, B. L. Articles by Bertozzi, C. R. Social Bookmarking                      What's this?

Function and Structure of a Prokaryotic Formylglycine-generating Enzyme^*

Brian L. Carlson¹, Edward R. Ballister^¶, Emmanuel Skordalakes², David S. King, Mark A. Breidenbach^¶, Sarah A. Gilmore, James M. Berger², and Carolyn R. Bertozzi^¶3

From the Departments of Molecular and Cell Biology and ^¶Chemistry, Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, California 94720

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-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 2.1Å 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.

Received for publication, January 9, 2008 , and in revised form, March 17, 2008.

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The atomic coordinates and structure factors (code 2Q17) have been deposited in the Protein Data Bank, Research Collaboratory for Structural Bioinformatics, Rutgers University, New Brunswick, NJ (http://www.rcsb.org/).

^* This work was supported, in whole or in part, by National Institutes of Health Grants AI051662 and GM059907 (to C. R. B.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains supplemental Figs. S1–S4 and Tables S1 and S2.

¹ Supported by a predoctoral fellowship from the National Science Foundation.

² Supported by National Institutes of Health Grant AI068135.

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³ To whom correspondence should be addressed: B84 Hildebrand Hall, University of California, Berkeley, CA 94720. Tel.: 510-643-1682; Fax: 510-643-2628; E-mail: crb{at}berkeley.edu.

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