Send to

Choose Destination
See comment in PubMed Commons below
Chem Biol. 2004 Apr;11(4):565-73.

A bacterial acetyltransferase capable of regioselective N-acetylation of antibiotics and histones.

Author information

Department of Biochemistry, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461 USA.


The Salmonella enterica chromosomally encoded AAC(6')-Iy has been shown to confer broad aminoglycoside resistance in strains in which the structural gene is expressed. The three-dimensional structures reported place the enzyme in the large Gcn5-related N-acetyltransferase (GNAT) superfamily. The structure of the CoA-ribostamycin ternary complex allows us to propose a chemical mechanism for the reaction, and comparison with the Mycobacterium tuberculosis AAC(2')-CoA-ribostamycin complex allows us to define how regioselectivity of acetylation is achieved. The AAC(6')-Iy dimer is most structurally similar to the Saccharomyces cerevisiae Hpa2-encoded histone acetyltransferase. We demonstrate that AAC(6')-Iy catalyzes both acetyl-CoA-dependent self-alpha-N-acetylation and acetylation of eukaryotic histone proteins and the human histone H3 N-terminal peptide. These structural and catalytic similarities lead us to propose that chromosomally encoded bacterial acetyltransferases, including those functionally identified as aminoglycoside acetyltransferases, are the evolutionary progenitors of the eukaryotic histone acetyltransferases.

[Indexed for MEDLINE]
Free full text
PubMed Commons home

PubMed Commons

How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science
    Loading ...
    Support Center