Mackenzie, Alasdair
- Department of Molecular Biology, Swedish University of Agricultural Sciences
Research article2010Peer reviewed
Mackenzie Alasdair K., Valegard Karin, Iqbal Aman, Caines Matthew E. C., Kershaw Nadia J., Jensen Susan E., Schofield Christopher J., Andersson Inger
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
clavulanic acid; beta-lactam; beta-lactamase inhibitor; oligopeptide-binding proteins; solute-binding proteins
Journal of Molecular Biology
2010, Volume: 396, number: 2, pages: 332-344 Publisher: Elsevier
Biochemistry and Molecular Biology
DOI: https://doi.org/10.1016/j.jmb.2009.11.045
https://res.slu.se/id/publ/28924