2Q7T
Crystal Structure of the F plasmid TraI Relaxase Domain with the Scissile Thymidine Base
Summary for 2Q7T
| Entry DOI | 10.2210/pdb2q7t/pdb |
| Related | 1a0i 1omh 1osb 1p4d 1qx0 2cdm 2q7u |
| Descriptor | Protein traI, MAGNESIUM ION, THYMIDINE-5'-PHOSPHATE, ... (4 entities in total) |
| Functional Keywords | relaxase, hydrolase, conjugation |
| Biological source | Escherichia coli |
| Total number of polymer chains | 2 |
| Total formula weight | 67075.36 |
| Authors | Lujan, S.A.,Redinbo, M.R. (deposition date: 2007-06-07, release date: 2008-05-20, Last modification date: 2023-08-30) |
| Primary citation | 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 Cited by 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: 17630285DOI: 10.1073/pnas.0702760104 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.42 Å) |
Structure validation
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