2PR8

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

Summary for 2PR8

• Entry DOI: 10.2210/pdb2pr8/pdb
• Descriptor: Aminoglycoside 6-N-acetyltransferase type Ib11, 4-(2-HYDROXYETHYL)-1-PIPERAZINE ETHANESULFONIC ACID (3 entities in total)
• Functional Keywords: gnat, aminoglycoside acetyltransferase, transferase
• Biological source: Salmonella typhimurium
• Total number of polymer chains: 2
• Total formula weight: 44237.39

Authors

Maurice, F.,Broutin, I.,Podglajen, I.,Benas, P.,Collatz, E.,Dardel, F. (deposition date: 2007-05-04, release date: 2008-04-08, Last modification date: 2024-02-21)

Primary citation

Maurice, F.,Broutin, I.,Podglajen, I.,Benas, P.,Collatz, E.,Dardel, F.
Enzyme structural plasticity and the emergence of broad-spectrum antibiotic resistance.
Embo Rep., 9:344-349, 2008

PubMed Abstract: 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.

PubMed: 18292754
DOI: 10.1038/embor.2008.9

Experimental method

X-RAY DIFFRACTION (2.1 Å)