InterPro domain: IPR005846

The alpha-D-phosphohexomutase superfamily is composed of four related enzymes, each of which catalyses a phosphoryl transfer on their sugar substrates: phosphoglucomutase (PGM), phosphoglucomutase/phosphomannomutase (PGM/PMM), phosphoglucosamine mutase (PNGM), and phosphoacetylglucosamine mutase (PAGM) [ 1 ]. PGM ( 5.4.2.2 ) converts D-glucose 1-phosphate into D-glucose 6-phosphate, and participates in both the breakdown and synthesis of glucose [ 2 ]. PGM/PMM ( 5.4.2.2 ; 5.4.2.8 ) are primarily bacterial enzymes that use either glucose or mannose as substrate, participating in the biosynthesis of a variety of carbohydrates such as lipopolysaccharides and alginate [ 3 , 4 ]. Both PNGM ( 5.4.2.3 ) and PAGM ( 5.4.2.10 ) are involved in the biosynthesis of UDP-N-acetylglucosamine [ 5 , 6 ].

Despite differences in substrate specificity, these enzymes share a similar catalytic mechanism, converting 1-phospho-sugars to 6-phospho-sugars via a biphosphorylated 1,6-phospho-sugar. The active enzyme is phosphorylated at a conserved serine residue and binds one magnesium ion; residues around the active site serine are well conserved among family members. The reaction mechanism involves phosphoryl transfer from the phosphoserine to the substrate to create a biophosphorylated sugar, followed by a phosphoryl transfer from the substrate back to the enzyme [ 7 ].

The structures of PGM and PGM/PMM have been determined, and were found to be very similar in topology. These enzymes are both composed of four domains and a large central active site cleft, where each domain contains residues essential for catalysis and/or substrate recognition. Domain I contains the catalytic phosphoserine, domain II contains a metal-binding loop to coordinate the magnesium ion, domain III contains the sugar-binding loop that recognises the two different binding orientations of the 1- and 6-phospho-sugars, and domain IV contains a phosphate-binding site required for orienting the incoming phospho-sugar substrate.

This entry represents domain III found in alpha-D-phosphohexomutase enzymes. This domain has a 3-layer alpha/beta/alpha topology.

1. Functional diversity of the phosphoglucomutase superfamily: structural implications. Protein Eng. 12, 737-46
2. Structure of rabbit muscle phosphoglucomutase refined at 2.4 A resolution. Acta Crystallogr. D Biol. Crystallogr. 53, 392-405
3. The reaction of phosphohexomutase from Pseudomonas aeruginosa: structural insights into a simple processive enzyme. J. Biol. Chem. 281, 15564-71
4. Structural basis of diverse substrate recognition by the enzyme PMM/PGM from P. aeruginosa. Structure 12, 55-63
5. Identification of the Pseudomonas aeruginosa glmM gene, encoding phosphoglucosamine mutase. J. Bacteriol. 182, 4453-7
6. Functional cloning and mutational analysis of the human cDNA for phosphoacetylglucosamine mutase: identification of the amino acid residues essential for the catalysis. Biochim. Biophys. Acta 1492, 369-76
7. Evolutionary trace analysis of the alpha-D-phosphohexomutase superfamily. Protein Sci. 13, 2130-8