2prb | pdb_00002prb

crystal structure of aminoglycoside acetyltransferase AAC(6')-Ib in complex whith coenzyme A

spinqualitylabelsall models 2prb, resolution 1.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2prb is a 1 chain structure with sequence from Salmonella enterica subsp. enterica serovar typhimurium. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: COA Related: 2pr8 Activity: Aminoglycoside N(6')-acetyltransferase, with EC number 2.3.1.82 Resources: FirstGlance, OCA, RCSB, PDBsum Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed The emergence of multi-resistant pathogenic bacteria is a worldwide health issue. Recently, clinical variants of a single antibiotic-modifying acetyltransferase, AAC(6')-Ib-a variant of aminoglycoside 6'-N-acetyltransferase-have been identified that confer extended resistance to most aminoglycosides and, more surprisingly, to structurally unrelated fluoroquinolones. The corresponding gene is carried by mobile genetic elements and is present in most multi-resistant pathogenic strains, hence making it a serious threat to current therapies. Here, we report the crystal structures of both narrow- and broad-spectrum resistance variants of this enzyme, which reveal the structural basis for the emergence of extended resistance. The active site shows an important plasticity and has adapted to new substrates by a large-scale gaping process. We have also obtained co-crystals with both substrates, and with a simple transition state analogue, which provides new clues for the design of inhibitors of this resistance mechanism. Enzyme structural plasticity and the emergence of broad-spectrum antibiotic resistance.,Maurice F, Broutin I, Podglajen I, Benas P, Collatz E, Dardel F EMBO Rep. 2008 Apr;9(4):344-9. Epub 2008 Feb 22. PMID:18292754 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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