Alpha-D-phosphohexomutase, alpha/beta/alpha I/II/III (IPR016055)
Short name: A-D-PHexomutase_a/b/a-I/II/III
- Alpha-D-phosphohexomutase, alpha/beta/alpha domain I (IPR005844)
- Alpha-D-phosphohexomutase, alpha/beta/alpha domain III (IPR005846)
- Phosphoglucomutase, alpha-D-glucose specific (IPR005852)
- Phosphoglucosamine mutase, bacterial type (IPR006352)
- Phosphoacetylglucosamine mutase (IPR016657)
- Phosphoglucosamine mutase, archaeal (IPR023666)
- Phosphoglucosamine mutase, archaeal type (IPR024086)
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) [PMID: 10506283]. PGM (EC:184.108.40.206) converts D-glucose 1-phosphate into D-glucose 6-phosphate, and participates in both the breakdown and synthesis of glucose [PMID: 15299905]. PGM/PMM (EC:220.127.116.11; EC:18.104.22.168) 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 [PMID: 16595672, PMID: 14725765]. Both PNGM (EC:22.214.171.124) and PAGM (EC:126.96.36.199) are involved in the biosynthesis of UDP-N-acetylglucosamine [PMID: 10913078, PMID: 11004509].
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 [PMID: 15238632].
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 superfamily represents domains I, II and III found in alpha-D-phosphohexomutase enzymes. All three domains share a 3-layer alpha/beta/alpha topology.
- SSF53738 (SSF53738)