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Publication Abstract from PubMed

Cells use the post-translational modification ADP-ribosylation to control a host of biological activities. In some pathogenic bacteria, an operon-encoded mono-ADP-ribosylation cycle mediates response to host-induced oxidative stress. In this system, reversible mono ADP-ribosylation of a lipoylated target protein represses oxidative stress response. An NAD+ -dependent sirtuin catalyzes the single ADP-ribose (ADPr) addition, while a linked macrodomain-containing protein removes the ADPr. Here we report the crystal structure of the sitruin-linked macrodomain protein from Staphylococcus aureus, SauMacro (also known as SAV0325) to 1.75-A resolution. The monomeric SauMacro bears a previously unidentified Zn2+ -binding site that putatively aids in substrate recognition and catalysis. An amino-terminal three-helix bundle motif unique to this class of macrodomain proteins provides a structural scaffold for the Zn2+ site. Structural features of the enzyme further indicate a cleft proximal to the Zn2+ binding site appears well suited for ADPr binding, while a deep hydrophobic channel in the protein core is suitable for binding the lipoate of the lipoylated protein target.

Structure of the sirtuin-linked macrodomain SAV0325 from Staphylococcus aureus.,Appel CD, Feld GK, Wallace BD, Williams RS Protein Sci. 2016 Jun 27. doi: 10.1002/pro.2974. PMID:27345688^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.