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  • The EMBO Journal (2009) 28, 2128 - 2142
  • doi:10.1038/emboj.2009.165

Published online: 25 June 2009

Structure and function of a complex between chorismate mutase and DAHP synthase: efficiency boost for the junior partner

Severin Sasso1,*, Mats Ökvist2,*, Kathrin Roderer1, Marianne Gamper1, Giosiana Codoni1, Ute Krengel2 and Peter Kast1

  1. Laboratory of Organic Chemistry, ETH Zurich, Zurich, Switzerland
  2. Department of Chemistry, University of Oslo, Oslo, Norway

Correspondence to:

Ute Krengel, Department of Chemistry, University of Oslo, NO-0315 Oslo, Norway. Tel.: +47 22 85 5461; Fax: +47 22 85 5441; E-mail: ute.krengel@kjemi.uio.no

Peter Kast, Laboratory of Organic Chemistry, ETH Zurich, HCI F333, Wolfgang-Pauli-Strasse 10, CH-8093 Zurich, Switzerland. Tel.: +41 44 632 2908; Fax: +41 44 633 1326; E-mail: kast@org.chem.ethz.ch

*These authors contributed equally to this work

Received 9 January 2009; Accepted 26 May 2009

Chorismate mutase catalyzes a key step in the shikimate biosynthetic pathway towards phenylalanine and tyrosine. Curiously, the intracellular chorismate mutase of Mycobacterium tuberculosis (MtCM; Rv0948c) has poor activity and lacks prominent active-site residues. However, its catalytic efficiency increases >100-fold on addition of DAHP synthase (MtDS; Rv2178c), another shikimate-pathway enzyme. The 2.35 Å crystal structure of the MtCM–MtDS complex bound to a transition-state analogue shows a central core formed by four MtDS subunits sandwiched between two MtCM dimers. Structural comparisons imply catalytic activation to be a consequence of the repositioning of MtCM active-site residues on binding to MtDS. The mutagenesis of the C-terminal extrusion of MtCM establishes conserved residues as part of the activation machinery. The chorismate-mutase activity of the complex, but not of MtCM alone, is inhibited synergistically by phenylalanine and tyrosine. The complex formation thus endows the shikimate pathway of M. tuberculosis with an important regulatory feature. Experimental evidence suggests that such non-covalent enzyme complexes comprising an AroQdelta subclass chorismate mutase like MtCM are abundant in the bacterial order Actinomycetales.

  • Keywords:

    • enzyme catalysis,
    • multi-enzyme complex,
    • Mycobacterium tuberculosis Rv0948c,
    • shikimate pathway,
    • X-ray crystal structure
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