title: Structural basis for phosphomannose isomerase activity in phosphoglucose isomerase from Pyrobaculum aerophilum: a subtle difference between distantly related enzymes.
abstract: The crystal structure of a dual-specificity phosphoglucose/phosphomannose isomerase from the crenarchaeon Pyrobaculum aerophilum (PaPGI/PMI) has been determined in complex with glucose 6-phosphate at 1.16 A resolution and with fructose 6-phosphate at 1.5 A resolution. Subsequent modeling of mannose 6-phosphate (M6P) into the active site of the enzyme shows that the PMI activity of this enzyme may be due to the additional space imparted by a threonine. In PGIs from bacterial and eukaryotic sources, which cannot use M6P as a substrate, the equivalent residue is a glutamine. The increased space may permit rotation of the C2-C3 bond in M6P to facilitate abstraction of a proton from C2 by Glu203 and, after a further C2-C3 rotation of the resulting cis-enediolate, re-donation of a proton to C1 by the same residue. A proline residue (in place of a glycine in PGI) may also promote PMI activity by positioning the C1-O1 region of M6P. Thus, the PMI reaction in PaPGI/PMI probably uses a cis-enediol mechanism of catalysis, and this activity appears to arise from a subtle difference in the architecture of the enzyme, compared to bacterial and eukaryotic PGIs.
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: D019843:Archaeal Proteins / Q000737:chemistry* / Q000378:metabolism; D001665:Binding Sites; D018360:Crystallography, X-Ray; D019298:Glucose-6-Phosphate / Q000737:chemistry / Q000378:metabolism; D005956:Glucose-6-Phosphate Isomerase / Q000737:chemistry* / Q000378:metabolism; D008024:Ligands; D008359:Mannose-6-Phosphate Isomerase / Q000737:chemistry* / Q000378:metabolism; D008360:Mannosephosphates / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation; D041543:Pyrobaculum / Q000201:enzymology*; D040681:Structural Homology, Protein; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
chemical_list: D019843:Archaeal Proteins; D008024:Ligands; D008360:Mannosephosphates; C027693:mannose-6-phosphate; D019298:Glucose-6-Phosphate; D008359:Mannose-6-Phosphate Isomerase; D005956:Glucose-6-Phosphate Isomerase