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Structure of the sirtuin‐linked macrodomain SAV0325 from Staphylococcus aureus
Author(s) -
Appel C. Denise,
Feld Geoffrey K.,
Wallace Bret D.,
Williams R. Scott
Publication year - 2016
Publication title -
protein science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.353
H-Index - 175
eISSN - 1469-896X
pISSN - 0961-8368
DOI - 10.1002/pro.2974
Subject(s) - biochemistry , binding site , nad+ kinase , protein structure , operon , active site , chemistry , biology , transferase , histone , nicotinamide adenine dinucleotide , scaffold protein , enzyme , biophysics , stereochemistry , escherichia coli , gene , signal transduction
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‐Å resolution. The monomeric SauMacro bears a previously unidentified Zn 2+ ‐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 Zn 2+ site. Structural features of the enzyme further indicate a cleft proximal to the Zn 2+ 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.