2Q7U

Crystal Structure of the F plasmid TraI Relaxase Domain with the Scissile Thymidine Base and Imidodiphosphate

2Q7U の概要

• エントリーDOI: 10.2210/pdb2q7u/pdb
• 関連するPDBエントリー: 1a0i 1omh 1osb 1p4d 1qx0 2cdm 2Q7T
• 分子名称: Protein traI, MAGNESIUM ION, IMIDO DIPHOSPHATE, ... (5 entities in total)
• 機能のキーワード: relaxase, hydrolase, conjugation, alternative initiation, atp-binding, dna-binding, helicase, nucleotide-binding, plasmid
• 由来する生物種: Escherichia coli
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 67226.03

構造登録者

Lujan, S.A.,Redinbo, M.R. (登録日: 2007-06-07, 公開日: 2008-05-20, 最終更新日: 2023-08-30)

主引用文献

Lujan, S.A.,Guogas, L.M.,Ragonese, H.,Matson, S.W.,Redinbo, M.R.
Disrupting antibiotic resistance propagation by inhibiting the conjugative DNA relaxase.
Proc.Natl.Acad.Sci.Usa, 104:12282-12287, 2007

PubMed Abstract: Conjugative transfer of plasmid DNA via close cell-cell junctions is the main route by which antibiotic resistance genes spread between bacterial strains. Relaxases are essential for conjugative transfer and act by cleaving DNA strands and forming covalent phosphotyrosine linkages. Based on data indicating that multityrosine relaxase enzymes can accommodate two phosphotyrosine intermediates within their divalent metal-containing active sites, we hypothesized that bisphosphonates would inhibit relaxase activity and conjugative DNA transfer. We identified bisphosphonates that are nanomolar inhibitors of the F plasmid conjugative relaxase in vitro. Furthermore, we used cell-based assays to demonstrate that these compounds are highly effective at preventing DNA transfer and at selectively killing cells harboring conjugative plasmids. Two potent inhibitors, clodronate and etidronate, are already clinically approved to treat bone loss. Thus, the inhibition of conjugative relaxases is a potentially novel antimicrobial approach, one that selectively targets bacteria capable of transferring antibiotic resistance and generating multidrug resistant strains.

PubMed: 17630285
DOI: 10.1073/pnas.0702760104

実験手法

X-RAY DIFFRACTION (3 Å)