title: Prediction of structure and functional residues for O-GlcNAcase, a divergent homologue of acetyltransferases.
abstract: N-Acetyl-beta-D-glucosaminidase (O-GlcNAcase) is a key enzyme in the posttranslational modification of intracellular proteins by O-linked N-acetylglucosamine (O-GlcNAc). Here, we show that this protein contains two catalytic domains, one homologous to bacterial hyaluronidases and one belonging to the GCN5-related family of acetyltransferases (GNATs). Using sequence and structural information, we predict that the GNAT homologous region contains the O-GlcNAcase activity. Thus, O-GlcNAcase is the first member of the GNAT family not involved in transfer of acetyl groups, adding a new mode of evolution to this large protein family. Comparison with solved structures of different GNATs led to a reliable structure prediction and mapping of residues involved in binding of the GlcNAc-modified proteins and catalysis.
authors.affiliation: Computational Molecular Biology Department, Max-Planck-Institute for Molecular Genetics, Ihnestr. 73, 14195 Berlin, Germany. joerg.schultz@molgen.mpg.de
authors.forename: Jörg
authors.initials: J
authors.lastname: Schultz
authors.forename: Birgit
authors.initials: B
authors.lastname: Pils
mesh_terms: D000595:Amino Acid Sequence; D020134:Catalytic Domain; D019143:Evolution, Molecular; D008969:Molecular Sequence Data; D017351:N-Acetylglucosaminyltransferases / Q000737:chemistry / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D013329:Structure-Activity Relationship
chemical_list: D017351:N-Acetylglucosaminyltransferases; C449880:O-GlcNAc transferase