4ht4

Molecular Basis of Vancomycin Resistance Transfer in Staphylococcus aureus

spinqualitylabelsall models 4ht4, resolution 2.91Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4ht4 is a 2 chain structure with sequence from Staphylococcus aureus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.907Å Ligands: CA, CL, MSE, NI Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q53632_STAAU Publication Abstract from PubMed 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. Molecular basis of antibiotic multiresistance transfer in Staphylococcus aureus.,Edwards JS, Betts L, Frazier ML, Pollet RM, Kwong SM, Walton WG, Ballentine WK 3rd, Huang JJ, Habibi S, Del Campo M, Meier JL, Dervan PB, Firth N, Redinbo MR Proc Natl Acad Sci U S A. 2013 Jan 28. PMID:23359708 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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