Biology, Mechanism, and Structure of Enzymes in the α-d-Phosphohexomutase Superfamily

• Published in: Advances in protein chemistry and structural biology Vol. 109; pp. 265 - 304
• Main Authors: Stiers, Kyle M, Muenks, Andrew G, Beamer, Lesa J
• Format: Journal Article
• Language: English
• Published: Netherlands 2017
• Subjects: Amino Acid Sequence; Animals; Bacteria - chemistry; Bacteria - enzymology; Bacteria - genetics; Bacteria - metabolism; Bacterial Infections - enzymology; Bacterial Infections - genetics; Bacterial Infections - metabolism; Catalytic Domain; Crystallography, X-Ray; Glucosephosphates - chemistry; Glucosephosphates - genetics; Glucosephosphates - metabolism; Humans; Metabolic Diseases - enzymology; Metabolic Diseases - genetics; Metabolic Diseases - metabolism; Mutation; Nuclear Magnetic Resonance, Biomolecular; Phosphoglucomutase - chemistry; Phosphoglucomutase - genetics; Phosphoglucomutase - metabolism; Protein Conformation; Sequence Alignment; Oligomers; Phosphorylation; Enzyme mechanism; Inherited disease; Protein flexibility; Phosphosugar; Missense variants; Conformational change; Crystal structure
• ISSN: 1876-1623; 1876-1631
• DOI: 10.1016/bs.apcsb.2017.04.005

Enzymes in the α-d-phosphohexomutases superfamily catalyze the reversible conversion of phosphosugars, such as glucose 1-phosphate and glucose 6-phosphate. These reactions are fundamental to primary metabolism across the kingdoms of life and are required for a myriad of cellular processes, ranging from exopolysaccharide production to protein glycosylation. The subject of extensive mechanistic characterization during the latter half of the 20th century, these enzymes have recently benefitted from biophysical characterization, including X-ray crystallography, NMR, and hydrogen-deuterium exchange studies. This work has provided new insights into the unique catalytic mechanism of the superfamily, shed light on the molecular determinants of ligand recognition, and revealed the evolutionary conservation of conformational flexibility. Novel associations with inherited metabolic disease and the pathogenesis of bacterial infections have emerged, spurring renewed interest in the long-appreciated functional roles of these enzymes.