title: A novel phosphoglucose isomerase (PGI)/phosphomannose isomerase from the crenarchaeon Pyrobaculum aerophilum is a member of the PGI superfamily: structural evidence at 1.16-A resolution.
abstract: The crystal structure of a dual specificity phosphoglucose isomerase (PGI)/phosphomannose isomerase from Pyrobaculum aerophilum (PaPGI/PMI) has been determined in native form at 1.16-A resolution and in complex with the enzyme inhibitor 5-phosphoarabinonate at 1.45-A resolution. The similarity of its fold, with the inner core structure of PGIs from eubacterial and eukaryotic sources, confirms this enzyme as a member of the PGI superfamily. The almost total conservation of amino acids in the active site, including the glutamate base catalyst, shows that PaPGI/PMI uses the same catalytic mechanisms for both ring opening and isomerization for the interconversion of glucose 6-phosphate (Glc-6-P) to fructose 6-phosphate (Fru-6-P). The lack of structural differences between native and inhibitor-bound enzymes suggests this activity occurs without any of the conformational changes that are the hallmark of the well characterized PGI family. The lack of a suitable second base in the active site of PaPGI/PMI argues against a PMI mechanism involving a trans-enediol intermediate. Instead, PMI activity may be the result of additional space in the active site imparted by a threonine, in place of a glutamine in other PGI enzymes, which could permit rotation of the C-2-C-3 bond of mannose 6-phosphate.
authors.affiliation: Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, South Carolina 29425, USA.
authors.forename: Michael K
authors.initials: MK
authors.lastname: Swan
authors.forename: Thomas
authors.initials: T
authors.lastname: Hansen
authors.forename: Peter
authors.initials: P
authors.lastname: Schönheit
authors.forename: Christopher
authors.initials: C
authors.lastname: Davies
mesh_terms: D000595:Amino Acid Sequence; D005956:Glucose-6-Phosphate Isomerase / Q000737:chemistry* / Q000378:metabolism*; D008359:Mannose-6-Phosphate Isomerase / Q000737:chemistry* / Q000378:metabolism*; D008969:Molecular Sequence Data; D005810:Multigene Family; D010428:Pentosephosphates / Q000378:metabolism; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D041543:Pyrobaculum / Q000201:enzymology*; D013379:Substrate Specificity
chemical_list: D010428:Pentosephosphates; C012188:arabinonate-5-phosphate; D008359:Mannose-6-Phosphate Isomerase; D005956:Glucose-6-Phosphate Isomerase