2XTX

Structure of QnrB1 (M102R-Trypsin Treated), a plasmid-mediated fluoroquinolone resistance protein

Summary for 2XTX

• Entry DOI: 10.2210/pdb2xtx/pdb
• Related: 2XTW 2XTY
• Descriptor: QNRB1, SULFATE ION (3 entities in total)
• Functional Keywords: cell cycle, pentapeptide repeat, prp, antibiotic resistance, right handed quadrilateral beta-helix
• Biological source: KLEBSIELLA PNEUMONIAE
• Total number of polymer chains: 2
• Total formula weight: 48496.28

Authors

Vetting, M.W.,Hegde, S.S.,Park, C.H.,Jacoby, G.A.,Hooper, D.C.,Blanchard, J.S. (deposition date: 2010-10-12, release date: 2010-10-20, Last modification date: 2024-05-08)

Primary citation

Vetting, M.W.,Hegde, S.S.,Wang, M.,Jacoby, G.A.,Hooper, D.C.,Blanchard, J.S.
Structure of Qnrb1, a Plasmid-Mediated Fluoroquinolone Resistance Factor.
J.Biol.Chem., 286:25265-, 2011

PubMed Abstract: QnrB1 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 β-helix with a highly asymmetric dimeric structure typical of PRP-topoisomerase poison resistance factors. The threading of pentapeptides into the β-helical fold is interrupted by two noncanonical 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 toward inhibition by quinolones, whereas deletion of the smaller lower loop drastically reduced the protective effect. These loops are conserved among all plasmid-based Qnr variants (QnrA, QnrC, QnrD, and QnrS) and some chromosomally encoded Qnr varieties. A mechanism in which PRP-topoisomerase poison resistance factors bind to and disrupt the quinolone-DNA-gyrase interaction is proposed.

PubMed: 21597116
DOI: 10.1074/JBC.M111.226936

Experimental method

X-RAY DIFFRACTION (2.2 Å)