Crystal structures of an oligopeptide-binding protein from the biosynthetic pathway of the beta-lactamase inhibitor clavulanic acid.

Journal of Molecular Biology
Alasdair K MackenzieInger Andersson

Abstract

Clavulanic acid (CA) is a clinically important beta-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), which 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 OppA2 bind di-/tripeptides containing arginine and certain nonapeptides including bradykinin. 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 A resolution, respectively. The overall fold of OppA2 consists of two lobes with a deep cavity in the center, 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 bradykini...Continue Reading

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Citations

Aug 17, 2010·Applied Microbiology and Biotechnology·Ju Yeon SongKye Joon Lee
Sep 6, 2012·Journal of Industrial Microbiology & Biotechnology·Susan E Jensen
Dec 7, 2013·Applied Microbiology and Biotechnology·R Álvarez-ÁlvarezP Liras
Nov 9, 2012·Natural Product Reports·Refaat B HamedChristopher J Schofield
Oct 4, 2021·Journal of Industrial Microbiology & Biotechnology·Paloma Liras, Juan F Martín

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