2XTY

Structure of QnrB1 (R167E-Trypsin Treated), a plasmid-mediated fluoroquinolone resistance protein

2XTY の概要

• エントリーDOI: 10.2210/pdb2xty/pdb
• 関連するPDBエントリー: 2XTW 2XTX
• 分子名称: QNRB1 (2 entities in total)
• 機能のキーワード: cell cycle, pentapeptide repeat, prp, antibiotic resistance, right handed quadrilateral beta-helix
• 由来する生物種: KLEBSIELLA PNEUMONIAE
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 48196.00

構造登録者

Vetting, M.W.,Hegde, S.S.,Park, C.H.,Jacoby, G.A.,Hooper, D.C.,Blanchard, J.S. (登録日: 2010-10-13, 公開日: 2010-10-27, 最終更新日: 2023-12-20)

主引用文献

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

実験手法

X-RAY DIFFRACTION (1.8 Å)