GlmU from Mycobacterium tuberculosis – Structure, Function, and the Role of Metal Ions in Catalysis

N-Acetylglucosamine-1-phosphate uridyltransferase (GlmU) forms a biological trimer. Each monomer has two independent domains that catalyze two independent enzymatic reactions. The C-terminal domain catalyzes an acetyltransfer reaction: The product of this reaction, N-acetylglucosamine-1-phosphate (GlcNAc-1-P), is subsequently utilized by the N-terminal domain to synthesize a sugar nucleotide, UDP-GlcNAc. The reaction catalyzed by the N-terminal domain, that is, the uridyltransfer reaction is While the acetyltransfer reaction catalyzed by the C-terminal domain is metal independent, the uridyltransfer reaction requires the binding of two Mg2+ ions at the active site, for stabilizing the substrates and for catalysis. The coordination chemistry of Mn2+ is similar to that of the Mg2+, and therefore Mn2+ too can catalyze this reaction effectively. Besides, Co2+ ions were also found to bind at the active site and catalyze the reaction. 3D Structure Three-dimensional structure of GlmU from Mycobacterium tuberculosis (GlmUMtb): Ribbon representation of a (a) monomer and (b) the trimer of GlmUMtb. Metal ions are shown as green spheres. Each monomer of the trimer is colored differently. The figures are generated using PyMOL.1 PDB code: 4G87. Keywords: enzyme; UDP-N-acetylglucosamine pyrophosphorylase; bifunctional GlmU; glucosamine-1-phosphate acetyltransferase; N-acetylglucosamine-1-phosphate uridylyltransferase; sugar nucleotidyl transferase