4HT4

Molecular Basis of Vancomycin Resistance Transfer in Staphylococcus aureus

4HT4 の概要

• エントリーDOI: 10.2210/pdb4ht4/pdb
• 分子名称: Nicking enzyme, DNA (28-MER), NICKEL (II) ION, ... (6 entities in total)
• 機能のキーワード: vancomycin resistance plasmid, dna relaxase, s. aureus, conjugative transfer, dna hairpin, hydrolase-dna complex, hydrolase/dna
• 由来する生物種: Staphylococcus aureus
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 32124.60

構造登録者

Edwards, J.S. (登録日: 2012-10-31, 公開日: 2013-01-30, 最終更新日: 2024-10-30)

主引用文献

Edwards, J.S.,Betts, L.,Frazier, M.L.,Pollet, R.M.,Kwong, S.M.,Walton, W.G.,Ballentine, W.K.,Huang, J.J.,Habibi, S.,Del Campo, M.,Meier, J.L.,Dervan, P.B.,Firth, N.,Redinbo, M.R.
Molecular basis of antibiotic multiresistance transfer in Staphylococcus aureus.
Proc.Natl.Acad.Sci.USA, 110:2804-2809, 2013

PubMed Abstract: Multidrug-resistant Staphylococcus aureus infections pose a significant threat to human health. Antibiotic resistance is most commonly propagated by conjugative plasmids like pLW1043, the first vancomycin-resistant S. aureus vector identified in humans. We present the molecular basis for resistance transmission by the nicking enzyme in S. aureus (NES), which is essential for conjugative transfer. NES initiates and terminates the transfer of plasmids that variously confer resistance to a range of drugs, including vancomycin, gentamicin, and mupirocin. The NES N-terminal relaxase-DNA complex crystal structure reveals unique protein-DNA contacts essential in vitro and for conjugation in S. aureus. Using this structural information, we designed a DNA minor groove-targeted polyamide that inhibits NES with low micromolar efficacy. The crystal structure of the 341-residue C-terminal region outlines a unique architecture; in vitro and cell-based studies further establish that it is essential for conjugation and regulates the activity of the N-terminal relaxase. This conclusion is supported by a small-angle X-ray scattering structure of a full-length, 665-residue NES-DNA complex. Together, these data reveal the structural basis for antibiotic multiresistance acquisition by S. aureus and suggest novel strategies for therapeutic intervention.

PubMed: 23359708
DOI: 10.1073/pnas.1219701110

実験手法

X-RAY DIFFRACTION (2.907 Å)