Structure of an acetyl-CoA binding protein from Staphylococcus aureus representing a novel subfamily of GCN5-related N-acetyltransferase-like proteins

  • John R. Cort
  • Theresa A. Ramelot
  • Diana Murray
  • Thomas B. Acton
  • Li-Chung Ma
  • Rong Xiao
  • Gaetano T. Montelione
  • Michael A. Kennedy


We have determined the solution NMR structure of SACOL2532, a putative GCN5-like N-acetyltransferase (GNAT) from Staphylococcus aureus. SACOL2532 was shown to bind both CoA and acetyl-CoA, and structures with and without bound CoA were determined. Based on analysis of the structure and sequence, a subfamily of small GCN5-related N-acetyltransferase (GNAT)-like proteins can be defined. Proteins from this subfamily, which is largely congruent with COG2388, are characterized by a cysteine residue in the acetyl-CoA binding site near the acetyl group, by their small size in relation to other GNATs, by a lack of obvious substrate binding site, and by a distinct conformation of bound CoA in relation to other GNATs. Subfamily members are found in many bacterial and eukaryotic genomes, and in some archaeal genomes. Whereas other GNATs transfer the acetyl group of acetyl-CoA directly to an aliphatic amine, the presence of the conserved cysteine residue suggests that proteins in the COG2388 GNAT-subfamily transfer an acetyl group from acetyl-CoA to one or more presently unidentified aliphatic amines via an acetyl (cysteine) enzyme intermediate. The apparent absence of a substrate-binding region suggests that the substrate is a macromolecule, such as another protein, or that a second protein subunit providing a substrate-binding region must combine with SACOL2532 to make a fully functional N-acetyl transferase.


Acetyl coenzyme A Acetyl enzyme Acyl enzyme GCN5 GNAT N-acetyltransferase 









Coenzyme A




GCN5-like N-acetyltransferase


Heteronuclear multiple quantum coherence


Heteronuclear single quantum coherence


2-(N-morpholino)ethanesulfonic acid


Nuclear magnetic resonance


Nuclear Overhauser effect (spectroscopy)


Root mean square deviation



This research was supported by a grant from the Protein Structure Initiative of the National Institutes of Health (U54 GM074958). NMR spectra were acquired in the Environmental Molecular Sciences Laboratory (a national scientific user facility sponsored by the U.S. Department of Energy Office of Biological and Environmental Research) located at Pacific Northwest National Laboratory and operated for DOE by Battelle (contract KP130103). We thank Luciano Mueller for assistance with the doubly-filtered 1H–1H NOESY and TOCSY experiments.


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Copyright information

© Springer Science+Business Media B.V. 2008

Authors and Affiliations

  • John R. Cort
    • 1
    • 2
    • 3
  • Theresa A. Ramelot
    • 3
    • 4
  • Diana Murray
    • 3
    • 5
  • Thomas B. Acton
    • 3
    • 6
  • Li-Chung Ma
    • 3
    • 6
  • Rong Xiao
    • 3
    • 6
  • Gaetano T. Montelione
    • 3
    • 6
    • 7
  • Michael A. Kennedy
    • 3
    • 4
  1. 1.Washington State University Tri-CitiesRichlandUSA
  2. 2.Biological Sciences DivisionPacific Northwest National LaboratoryRichlandUSA
  3. 3.Northeast Structural Genomics Consortium (NESG)
  4. 4.Department of Chemistry and BiochemistryMiami UniversityOxfordUSA
  5. 5.Department of PharmacologyColumbia UniversityNew York CityUSA
  6. 6.Center for Advanced Biotechnology and Medicine, Department of Molecular Biology and BiochemistryRutgers UniversityPiscatawayUSA
  7. 7.Department of Biochemistry, Robert Wood Johnson Medical SchoolUniversity of Medicine and Dentistry of New JerseyPiscatawayUSA

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