title: The pentacovalent phosphorus intermediate of a phosphoryl transfer reaction.
abstract: Enzymes provide enormous rate enhancements, unmatched by any other type of catalyst. The stabilization of high-energy states along the reaction coordinate is the crux of the catalytic power of enzymes. We report the atomic-resolution structure of a high-energy reaction intermediate stabilized in the active site of an enzyme. Crystallization of phosphorylated beta-phosphoglucomutase in the presence of the Mg(II) cofactor and either of the substrates glucose 1-phosphate or glucose 6-phosphate produced crystals of the enzyme-Mg(II)-glucose 1,6-(bis)phosphate complex, which diffracted x-rays to 1.2 and 1.4 angstroms, respectively. The structure reveals a stabilized pentacovalent phosphorane formed in the phosphoryl transfer from the C(1)O of glucose 1,6-(bis)phosphate to the nucleophilic Asp8 carboxylate.
authors.affiliation: Department of Physiology and Biophysics, Boston University School of Medicine, Boston, MA 02118-2394, USA.
authors.forename: Sushmita D
authors.initials: SD
authors.lastname: Lahiri
authors.forename: Guofeng
authors.initials: G
authors.lastname: Zhang
authors.forename: Debra
authors.initials: D
authors.lastname: Dunaway-Mariano
authors.forename: Karen N
authors.initials: KN
authors.lastname: Allen
mesh_terms: D001665:Binding Sites; D002384:Catalysis; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003460:Crystallization; D018360:Crystallography, X-Ray; D019298:Glucose-6-Phosphate / Q000378:metabolism; D005958:Glucosephosphates / Q000737:chemistry / Q000378:metabolism; D013294:Lactococcus lactis / Q000201:enzymology; D008024:Ligands; D008274:Magnesium / Q000737:chemistry; D010710:Phosphates / Q000737:chemistry; D010733:Phosphoglucomutase / Q000737:chemistry* / Q000378:metabolism*; D010753:Phosphoranes / Q000737:chemistry; D010758:Phosphorus / Q000737:chemistry*; D010766:Phosphorylation; D011487:Protein Conformation; D017434:Protein Structure, Tertiary
chemical_list: D005958:Glucosephosphates; D008024:Ligands; D010710:Phosphates; D010753:Phosphoranes; D010758:Phosphorus; D019298:Glucose-6-Phosphate; C031590:glucose-1-phosphate; D010733:Phosphoglucomutase; D008274:Magnesium