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J. Biol. Chem., Vol. 283, Issue 10, 6467-6475, March 7, 2008

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The Violacein Biosynthetic Enzyme VioE Shares a Fold with Lipoprotein Transporter Proteins^*

Katherine S. Ryan¹, Carl J. Balibar², Kaitlyn E. Turo^¶3, Christopher T. Walsh, and Catherine L. Drennan^¶4

From the Department of Biology and ^¶Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139 and Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115

VioE, an unusual enzyme with no characterized homologues, plays a key role in the biosynthesis of violacein, a purple pigment with antibacterial and cytotoxic properties. Without bound cofactors or metals, VioE, from the bacterium Chromobacterium violaceum, mediates a 1,2 shift of an indole ring and oxidative chemistry to generate prodeoxyviolacein, a precursor to violacein. Our 1.21 Å resolution structure of VioE shows that the enzyme shares a core fold previously described for lipoprotein transporter proteins LolA and LolB. For both LolB and VioE, a bound polyethylene glycol molecule suggests the location of the binding and/or active site of the protein. Mutations of residues near the bound polyethylene glycol molecule in VioE have identified the active site and five residues important for binding or catalysis. This structural and mutagenesis study suggests that VioE acts as a catalytic chaperone, using a fold previously associated with lipoprotein transporters to catalyze the production of its prodeoxyviolacein product.

Received for publication, October 16, 2007 , and in revised form, December 13, 2007.

The atomic coordinates and structure factors (code 3BMZ) 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 part by National Institutes of Health Grants GM65337 (to C. L. D.) and GM 20011 (to C. T. W.) and the MIT Center for Environmental Health Sciences NIEHS P30 ES002109. This work was also supported in part by National Science Foundation Grant 0070319, National Institutes of Health Grant GM68762, and other funds from the National Institutes of Health. 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 Table S1 and supplemental Figs. S1-S7.

¹ Supported by a Howard Hughes Medical Institute Predoctoral Fellowship.

² Supported by a National Science Foundation Graduate Research Fellowship.

³ Supported by a Douglass College Science, Technology, Engineering, and Math Summer Research Experience Grant (Rutgers University) and Howard Hughes Medical Institute-MIT Summer Research Experience in Chemical Biology Grant 52005719.

⁴ To whom correspondence should be addressed. Tel.: 617-253-5622; Fax: 617-258-7847; E-mail: cdrennan{at}mit.edu.

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