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Abstract

Clavulanic acid (CA) is a clinically important ß-lactamase inhibitor that is produced by fermentation of Streptomyces clavuligerus. The CA biosynthesis pathway starts from arginine and glyceraldehyde-3-phosphate, and proceeds via (3S,5S)-clavaminic acid, which is converted to (3R,5R)-clavaldehyde, the immediate precursor of (3R,5R)-CA. Open reading frames 7 (orf7) and 15 (orf15) of the CA biosynthesis cluster encode oligopeptide binding proteins (OppA1 and OppA2), that are essential for CA biosynthesis. OppA1/2 are proposed to be involved in the binding and/or transport of peptides across the S. clavuligerus cell membrane. Peptide binding assays reveal that recombinant OppA1 and 2 bind di/tri peptides containing arginine. Crystal structures of OppA2 in its apo form and in complex with arginine or bradykinin were solved to 1.45, 1.7, and 1.7 Å resolution, respectively. The overall fold of OppA2 consists of two lobes with a deep cavity in the centre, as observed for other oligopeptide binding proteins. The large cavity creates a peptide/arginine binding cleft. The crystal structures of OppA2 in complex with arginine or bradykinin reveal that the C-terminal arginine of bradykinin binds similarly to arginine. The results are discussed in terms of the possible roles of OppA1/2 in CA biosynthesis

Keywords

clavulanic acid; beta-lactam; beta-lactamase inhibitor; oligopeptide-binding proteins; solute-binding proteins

Published in

Journal of Molecular Biology
2010, volume: 396, number: 2, pages: 332-344
Publisher: Elsevier

SLU Authors

  • Mackenzie, Alasdair

    • Department of Molecular Biology, Swedish University of Agricultural Sciences

  • Valegård, Karin

    • Department of Molecular Biology, Swedish University of Agricultural Sciences

  • Andersson, Inger

    • Department of Molecular Biology, Swedish University of Agricultural Sciences

UKÄ Subject classification

Biochemistry
Molecular Biology

Publication identifier

  • DOI: https://doi.org/10.1016/j.jmb.2009.11.045

Permanent link to this page (URI)

https://res.slu.se/id/publ/28924