Journal of Structural and Functional Genomics

, Volume 14, Issue 3, pp 97–108 | Cite as

Biophysical analysis of the putative acetyltransferase SACOL2570 from methicillin-resistant Staphylococcus aureus

  • Hai-Bin Luo
  • Aleksandra A. Knapik
  • Janusz J. Petkowski
  • Matthew Demas
  • Igor A. Shumilin
  • Heping Zheng
  • Maksymilian Chruszcz
  • Wladek Minor


Methicillin-resistant Staphylococcus aureus (MRSA) is a major cause of a myriad of insidious and intractable infections in humans, especially in patients with compromised immune systems and children. Here, we report the apo- and CoA-bound crystal structures of a member of the galactoside acetyltransferase superfamily from methicillin-resistant S. aureus SACOL2570 which was recently shown to be down regulated in S. aureus grown in the presence of fusidic acid, an antibiotic used to treat MRSA infections. SACOL2570 forms a homotrimer in solution, as confirmed by small-angle X-ray scattering and dynamic light scattering. The protein subunit consists of an N-terminal alpha-helical domain connected to a C-terminal LβH domain. CoA binds in the active site formed by the residues from adjacent LβH domains. After determination of CoA-bound structure, molecular dynamics simulations were performed to model the binding of AcCoA. Binding of both AcCoA and CoA to SACOL2570 was verified by isothermal titration calorimetry. SACOL2570 most likely acts as an acetyltransferase, using AcCoA as an acetyl group donor and an as-yet-undetermined chemical moiety as an acceptor. SACOL2570 was recently used as a scaffold for mutations that lead the generation of cage-like assemblies, and has the potential to be used for the generation of more complex nanostructures.


Galactoside acetyltransferases GAT Methicillin-resistant Staphylococcus aureus (MRSA) subsp. COL Molecular dynamics Small-angle X-ray scattering Crystal structure 



Methicillin-resistant Staphylococcus aureus


Galactoside acetyltransferase


Small-angle X-ray scattering


Dynamic light scattering


Molecular dynamics


Protein Data Bank


Center for Structural Genomics of Infectious Diseases


Isothermal titration calorimetry


Root mean square deviation



We thank Matthew D. Zimmerman, David Cooper and Dominika Borek for their help in this study and for critical comments on the manuscript. This research was funded by the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services under Contract No. HHSN272200700058C), Natural Science Foundation of China (21103234), and Fundamental Research Funds for the Central Universities of China (11ykzd05). The diffraction data were collected at the beam lines 19-ID, 19-BM, and 21-ID at Argonne National Laboratory. Argonne is operated by University of Chicago Argonne, LLC, for the US Department of Energy, Office of Biological and Environmental Research under contract DE-AC02-06CH11357. Use of the LS-CAT Sector 21 was supported by the Michigan Economic Development Corporation and the Michigan Technology Tri-Corridor for the support of this research program (Grant 085P1000817). We would like to acknowledge Dr. Nicholas E. Sherman, the director of the W. M. Keck Biomedical Mass Spectrometry Laboratory is funded by a grant from the University of Virginia Pratt Fund through the School of Medicine.

Supplementary material

10969_2013_9158_MOESM1_ESM.pdf (530 kb)
Supplementary material 1 (PDF 529 kb)


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Copyright information

© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  • Hai-Bin Luo
    • 1
    • 2
    • 4
  • Aleksandra A. Knapik
    • 1
    • 4
  • Janusz J. Petkowski
    • 1
  • Matthew Demas
    • 1
  • Igor A. Shumilin
    • 1
    • 4
  • Heping Zheng
    • 1
    • 4
  • Maksymilian Chruszcz
    • 1
    • 3
    • 4
  • Wladek Minor
    • 1
    • 4
  1. 1.Department of Molecular Physiology and Biological PhysicsUniversity of VirginiaCharlottesvilleUSA
  2. 2.School of Pharmaceutical SciencesSun Yat-Sen UniversityGuangzhouChina
  3. 3.Department of Chemistry and BiochemistryUniversity of South CarolinaColumbiaUSA
  4. 4.Center for Structural Genomics of Infectious DiseasesCharlottesvilleUSA

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