📄 Macro domain from middle east respiratory syndrome coronavirus (MERS-CoV) is an efficient ADP-ribose binding module: Crystal structure and biochemical studies

© 2016 by The American Society for Biochemistry and Molecular Biology, Inc. The newly emerging Middle East respiratory syndrome coronavirus (MERS-CoV) encodes the conserved macro domain within non-structural protein 3. However, the precise biochemical function and structure of the macro domain is unclear. Using differential scanning fluorimetry and isothermal titration calorimetry, we characterized the MERS-CoV macro domain as a more efficient adenosine diphosphate (ADP)-ribose binding module than macro domains from other Co. Vs. Furthermore, the crystal structure of the MERS-CoV macro domain was determined at 1.43-Å resolution in complex with ADP-ribose. Comparison of macro domains from MERS-CoV and other human Co. Vs revealed structural differences in the α1 helix alters how the conserved Asp-20 interacts with ADP-ribose and may explain the efficient binding of the MERS-CoV macro domain to ADP-ribose. This study provides structural and biophysical bases to further evaluate the role of the MERS-CoV macro domain in the host response via ADP-ribose binding but also as a potential target for drug design.

keywords 🔗 syndrome coronavirus (1074) 🔗 drug design (36) 🔗 respiratory syndrome (2004) 🔗 crystal structure (114)

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