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  • The EMBO Journal (2002) 21, 3245 - 3254
  • doi:10.1093/emboj/cdf298

Structural analysis of two enzymes catalysing reverse metabolic reactions implies common ancestry

Olga Mayans1,2, Andreas Ivens3,4, L.Johan Nissen1, Kasper Kirschner3 and Matthias Wilmanns1

  1. EMBL Hamburg Outstation c/o DESY, Notkestrasse 85, D-22603 Hamburg, Germany
  2. Present address: Department of Structural Biology, Biozentrum, University of Basel, Klingelbergstrasse 70, CH-4056 Basel, Switzerland
  3. Department of Biophysical Chemistry, Biozentrum, University of Basel, Klingelbergstrasse 70, CH-4056 Basel, Switzerland
  4. Present address: Universität zu Köln, Institut für Biochemie, Otto-Fischer-Strasse 12–14, D-50674 Köln, Germany

Correspondence to:

Matthias Wilmanns, E-mail: wilmanns@embl-hamburg.de

Received 17 January 2002; Accepted 22 April 2002; Revised 18 April 2002

The crystal structure of the dimeric anthranilate phosphoribosyltransferase (AnPRT) reveals a new category of phosphoribosyltransferases, designated as class III. The active site of this enzyme is located within the flexible hinge region of its two-domain structure. The pyrophosphate moiety of phosphoribosylpyrophosphate is co-ordinated by a metal ion and is bound by two conserved loop regions within this hinge region. With the structure of AnPRT available, structural analysis of all enzymatic activities of the tryptophan biosynthesis pathway is complete, thereby connecting the evolution of its enzyme members to the general development of metabolic processes. Its structure reveals it to have the same fold, topology, active site location and type of association as class II nucleoside phosphorylases. At the level of sequences, this relationship is mirrored by 13 structurally invariant residues common to both enzyme families. Taken together, these data imply common ancestry of enzymes catalysing reverse biological processes—the ribosylation and deribosylation of metabolic pathway intermediates. These relationships establish new links for enzymes involved in nucleotide and amino acid metabolism.

  • Keywords:

    • enzyme evolution,
    • nucleoside phosphorylase,
    • nucleotide salvage,
    • phosphoribosyltransferase,
    • tryptophan biosynthesis