2pr8: Difference between revisions

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[[Image:2pr8.jpg|left|200px]]
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{{STRUCTURE_2pr8|  PDB=2pr8  |  SCENE=  }}  
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'''crystal structure of aminoglycoside N-acetyltransferase AAC(6')-Ib11'''
===crystal structure of aminoglycoside N-acetyltransferase AAC(6')-Ib11===




==Overview==
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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.
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{{ABSTRACT_PUBMED_18292754}}


==About this Structure==
==About this Structure==
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[[Category: Aminoglycoside acetyltransferase]]
[[Category: Aminoglycoside acetyltransferase]]
[[Category: Gnat]]
[[Category: Gnat]]
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jul  2 21:23:56 2008''

Revision as of 18:23, 2 July 2008

File:2pr8.png

Template:STRUCTURE 2pr8

crystal structure of aminoglycoside N-acetyltransferase AAC(6')-Ib11

Template:ABSTRACT PUBMED 18292754

About this Structure

2PR8 is a Single protein structure of sequence from Salmonella typhimurium. Full crystallographic information is available from OCA.

Reference

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):344-349. Epub 2008 Feb 22. PMID:18292754

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