The crystal structures of apo and complexed Saccharomyces cerevisiae GNA1 shed light on the catalytic mechanism of an amino-sugar N-acetyltransferase

The yeast enzymes involved in UDP-GlcNAc biosynthesis are potential targets for antifungal agents, GNA1, a novel member of the Gcn5-related N-acetyltr ansferase (GNAT) superfamily, participates in UDP-GlcNAc biosynthesis by ca talyzing the formation of GlcNAc6P from AcCoA and GlcN6P. We have solved th ree crystal structures corresponding to the apo Saccharomyces cerevisiae GN A1, the GNA1-AcCoA, and the GNA1-CoA-GlcNAc6P complexes and have refined th em to 2.4, 1.3, and 1.8 Angstrom resolution, respectively. These structures not only reveal a stable, beta -intertwined, dimeric assembly with the Glc NAc6P binding site located at the dimer interface but also shed light on th e catalytic machinery of GNA1 at an atomic level. Hence, they broaden our u nderstanding of structural features required for GNAT activity, provide str uctural details for related aminoglycoside N-acetyltransferases, and highli ght the adaptability of the GNAT superfamily members to acquire various spe cificities.