title: The crystal structure of human UDP-glucose pyrophosphorylase reveals a latch effect that influences enzymatic activity.
abstract: UGPase (UDP-glucose pyrophosphorylase) is highly conserved among eukaryotes. UGPase reversibly catalyses the formation of UDP-glucose and is critical in carbohydrate metabolism. Previous studies have mainly focused on the UGPases from plants, fungi and parasites, and indicate that the regulatory mechanisms responsible for the enzyme activity vary among different organisms. In the present study, the crystal structure of hUGPase (human UGPase) was determined and shown to form octamers through end-to-end and side-by-side interactions. The observed latch loop in hUGPase differs distinctly from yUGPase (yeast UGPase), which could explain why hUGPase and yUGPase possess different enzymatic activities. Mutagenesis studies showed that both dissociation of octamers and mutations of the latch loop can significantly affect the UGPase activity. Moreover, this latch effect is also evolutionarily meaningful in UGPase from different species.
authors: State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing, P.R. China.
authors: Quan
authors: Q
authors: Yu
authors: Xiaofeng
authors: X
authors: Zheng
mesh_terms: D000595:Amino Acid Sequence; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D019143:Evolution, Molecular; D006801:Humans; D007700:Kinetics; D046529:Microscopy, Electron, Transmission; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D050505:Mutant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure; D054730:Protein Interaction Domains and Motifs; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure; D017386:Sequence Homology, Amino Acid; D005957:UTP-Glucose-1-Phosphate Uridylyltransferase / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure
chemical_list: D050505:Mutant Proteins; D011994:Recombinant Proteins; D029701:Saccharomyces cerevisiae Proteins; D005957:UTP-Glucose-1-Phosphate Uridylyltransferase