Structural highlights
Publication Abstract from PubMedQnrB1 is a plasmid-encoded pentapeptide repeat protein (PRP) that confers a moderate degree of resistance to fluoroquinolones. Its gene was cloned into an expression vector with an N-terminal polyhistidine tag, and the protein was purified by nickel affinity chromatography. The structure of QnrB1 was determined by a combination of trypsinolysis, surface mutagenesis, and single anomalous dispersion phasing. QnrB1 folds as a right-handed quadrilateral beta-helix with a highly asymmetric dimeric structure typical of pentapeptide repeat protein topoisomerase-poison resistance factors (PRP-TPRF). The threading of pentapeptides into the beta-helical fold is interrupted by two non-canonical PRP sequences that produce outward projecting loops that interrupt the regularity of the PRP surface. Deletion of the larger upper loop eliminated the protective effect of QnrB1 on DNA gyrase towards inhibition by quinolones, while deletion of the smaller lower loop drastically reduced the protective effect. These loops are conserved among all plasmid-based Qnr variants (QnrA, QnrC, QnrD, QnrS) and some chromosomally encoded Qnr varieties. A mechanism in which PRP-TPRFs bind to and disrupt the quinolone-DNA-gyrase interaction is proposed. Structure of QnrB1, a plasmid-mediated fluoroquinolone resistance factor.,Vetting MW, Hegde SS, Wang M, Jacoby GA, Hooper DC, Blanchard JS J Biol Chem. 2011 May 19. PMID:21597116[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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