1S5K

Aminoglycoside N-Acetyltransferase AAC(6')-Iy in Complex with CoA and N-terminal His(6)-tag (crystal form 1)

Summary for 1S5K

• Entry DOI: 10.2210/pdb1s5k/pdb
• Related: 1S3Z
• Descriptor: aminoglycoside 6'-N-acetyltransferase, SULFATE ION, COENZYME A (3 entities in total)
• Functional Keywords: gnat, n-acetyltransferase, acetyltransferase, aminoglycoside, coa, transferase
• Biological source: Salmonella enteritidis
• Total number of polymer chains: 2
• Total formula weight: 38841.05

Authors

Vetting, M.W.,Magnet, S.,Nieves, E.,Roderick, S.L.,Blanchard, J.S. (deposition date: 2004-01-21, release date: 2004-05-18, Last modification date: 2024-02-14)

Primary citation

Vetting, M.W.,Magnet, S.,Nieves, E.,Roderick, S.L.,Blanchard, J.S.
A bacterial acetyltransferase capable of regioselective N-acetylation of antibiotics and histones
Chem.Biol., 11:565-573, 2004

PubMed Abstract: 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.

PubMed: 15123251
DOI: 10.1016/j.chembiol.2004.03.017

Experimental method

X-RAY DIFFRACTION (2.4 Å)