1.1.1.22 evolution the enzyme belongs to the the UGDH family of proteins -, 739891 1.1.1.22 evolution the N- and C-terminal domains of UgdG share structural features with ancient mitochondrial ribonucleases named MAR. MARs are present in lower eukaryotic microorganisms, have a Rossmannoid-fold and belong to the isochorismatase superfamily -, 739981 1.1.1.22 malfunction Haloferax volcanii cells deleted of HVO_1531 present a modified S-layer -, 728319 1.1.1.22 malfunction mutant dimeric species of UGDH have reduced activity in vitro and in supporting hyaluronan production by cultured cells. The purified enzymes reveal a significant decrease in the enzymatic activity of the obligate dimer and hexamer mutants. Both T325A and T325D mutants were significantly less efficient in promoting downstream hyaluronan production by HEK293 cells 740715 1.1.1.22 malfunction UGDH protein level in rat osteoarthritis cartilage are much lower than the corresponding controls and negatively correlated to the degree of osteoarthritis -, 739967 1.1.1.22 malfunction UGDH specific siRNAs markedly inhibits UGDH mRNA and protein expression, and leads to an obvious suppression of proteoglycans synthesis in human articular chondrocytes. UGDH protein level in human osteoarthritis cartilage are much lower than the corresponding controls and negatively correlated to the degree of osteoarthritis. Interleukin-1beta inhibits UGDH gene expression through modulating UGDH transregulators and the downstream signaling cascades, including the SAP/JNK and p38 MAPK pathways which might be involved in the proteoglycans loss of osteoarthritis cartilage and contribute to the osteoarthritis pathogenesis 739967 1.1.1.22 metabolism enzyme displays a NAD+-dependent SN2 mechanism. The first oxidation involves the nucleophilic addition of the essential Cys residue. The acceptor of C6-OH of UDP-glucose is an ordered H2O molecule. The second NADH is released after hydrolysis of the thioester intermediate 761284 1.1.1.22 metabolism in the Haloferax volcanii archaeal glycosylation pathway, Agl, responsible for the assembly and attachment of an Asn-linked pentasaccharide, enzyme AglM acts as a UDP-glucose dehydrogenase, converting UDP-glucose into UDP-glucuronic acid -, 740935 1.1.1.22 metabolism the enzyme participates in sucrose/polysaccharide metabolism and cell wall biosynthesis 740128 1.1.1.22 additional information dysregulated expression of UGDH can promote the development of androgen independent tumor cell growth by increasing available levels of intracellular androgen. UGDH activity is the rate limiting factor in solubilization of excess androgen from prostate tumor cells, overview 711665 1.1.1.22 additional information enzyme Ugd from Escherichia coli K-12 can functionally replace enzyme Ugd from Escherichia coli serotype K30 in biosynthesis of K30 capsular polysaccharide 740710 1.1.1.22 additional information mutation in either ugd leads to activation of RpoE, an extracytoplasmic function sigma factor that is activated by protein misfolding and alterations in cell surface structure in other bacteria. Activation of RpoE or RpoE overexpression causes inhibition of FlhDC and hemolysin expression 710889 1.1.1.22 additional information Sequence and structure comparison of UDP-glucose dehydrogenase AglM from Haloferax volcanii and VNG1048G from Halobacterium salinarum, homology modelling, overview -, 740935 1.1.1.22 additional information surface-exposed residues in homology models of the UDP-glucose dehydrogenase reveals the more acidic and less basic VNG1048G surface, explaining the salt-dependence of the Halobacterium salinarum enzyme. Sequence and structure comparison of UDP-glucose dehydrogenase AglM from Haloferax volcanii and VNG1048G from Halobacterium salinarum, homology modelling, overview -, 740935 1.1.1.22 additional information the active site of UgdG bound to UDP-Glc and coenzyme NADH contains 6 highly conserved residues: Thr122, Glu151, Lys207, Asn211, Cys263 and Asp267. Residue Cys263 is a clear candidate for the catalytic nucleophile of the reaction. Tyr10 plays a catalytic role in the final hydrolysis of UDP-Glc -, 739891 1.1.1.22 physiological function enzyme AglM can be functionally replaced by another UDP-glucose dehydrogenase, VNG1048G, in vivo -, 740935 1.1.1.22 physiological function enzyme displays hysteresis, observed as a lag in progress curves, and is sensitive to product inhibition during the lag. The inhibition results in a systematic decrease in steady-state velocity and makes the lag appear to have a second-order dependence on enzyme concentration.The lag is in fact due to a substrate and cofactor-induced isomerization of the enzyme. The cofactor binds to the enzyme:substrate complex with negative cooperativity, suggesting that the isomerization may be related to the formation of an asymmetric enzyme complex. The hysteresis may be the consequence of a functional adaptation, by slowing the response of the enzyme to sudden increases in the flux of substrate, the other biochemical pathways that use this important metabolite will have a competitive edge 724370 1.1.1.22 physiological function enzyme is involved in capsular polysaccharide biosynthesis -, 760612 1.1.1.22 physiological function enzyme VNG1048G can functionally replace another UDP-glucose dehydrogenase AglM in vivo. In Halobacterium salinarum, where glycoproteins are modified by an N-linked glycan of similar composition, gene VNG1048G is not only found within a cluster of N-glycosylation-related genes reminiscent of the genomic region surrounding its Haloferax volcanii counterpart AglM but can also functionally replace gene aglM in a Haloferax volcanii strain lacking the gene -, 740935 1.1.1.22 physiological function epirubicin accumulation increases and apoptosis decreases during UGDH knockdown. Hyaluronan-coated matrix increases and a positive modulation of autophagy is detected. Higher levels of UGDH are correlated with worse prognosis in triple-negative breast cancer patients that receive chemotherapy. High expression of UGDH is found in tumoral tissue from HER2--patients. UGDH knockdown contributes to epirubicin resistance 760676 1.1.1.22 physiological function in breast cancer cells, depletion of the hyaluronic acid precursor UDP-glucuronic acid is sufficient to inhibit several mesenchymal-like properties including cellular invasion and colony formation in vitro, as well as tumor growth and metastasis in vivo. Depletion of UDP-glucuronic acid alters the expression of PPAR-gamma target genes and increases PPAR-gamma DNA binding activity 762065 1.1.1.22 physiological function in Escherichia coli K-12, Ugd is important for biosynthesis of the environmentally regulated exopolysaccharide known as colanic acid, whereas in other Escherichia coli isolates, the same enzyme is required for production of the constitutive group 1 capsular polysaccharides, which act as virulence determinants 740710 1.1.1.22 physiological function in Escherichia coli serotype K30, the enzyme is required for production of the constitutive group 1 capsular polysaccharides, which act as virulence determinants 740710 1.1.1.22 physiological function knocking out UGDH in highly metastatic 6DT-1 breast cancer cells impairs migration ability without affecting in vitro proliferation. UGDH-KO results in significantly decreased metastatic capacity in vivo when the cells are orthotopically injected in syngeneic mice 760809 1.1.1.22 physiological function precise allelic exchange mutagenesis of isoform hasB in strain 5448, a representative of the globally disseminated M1T1 serotype, does not abolish hyaluronic acid capsule synthesis due to presence of paralog HasB2. Mutagenesis of HasB2 alone slightly decreases capsule abundance. A HasB HasB2 double mutant becomes completely acapsular -, 725276 1.1.1.22 physiological function the ectopic overexpression of UGDH4 in Arabidopsis thaliana significantly increases the contents of hemicellulose and soluble sugar 762397 1.1.1.22 physiological function the enzme synthesize UDP-glucuronate, a key sugar nucleotide involved in biosynthesis of the plant cell wall, the LgUGDH gene plays a role in controlling the biosynthesis of secondary cell walls 740128 1.1.1.22 physiological function the enzyme is involved in protein N-glycosylation -, 728319 1.1.1.22 physiological function the enzyme is involved in the biosnthesis of the Ss sphingan biopolymer -, 739891 1.1.1.22 physiological function the enzyme provides UDP-glucuronic acid for the synthesis of the exopolysaccharide gellan -, 739981 1.1.1.22 physiological function transgenic Arabidopsis lines overexpressing GH_D12G1806 have longer root lengths and higher gene expression level than the wild-type plants of Columbia-0. At flowering stage, the number of trichomes on the sepals of transgenic lines increases significantly, to about 155% of that of the control plants. Compared with the Col-0, most of the trichomes on the main stem of transgenic lines show bifurcated phenotypes 761138 1.1.1.22 physiological function UDP-glucose dehydrogenase activity and optimal downstream cellular function require dynamic reorganization at the dimer-dimer subunit interfaces 740715 1.1.1.22 physiological function UDP-glucose dehydrogenase is responsible for the NAD-dependent twofold oxidation of UDP-glucose to UDP-glucuronic acid, one of the key components for gellan biosynthesis -, 710762 1.1.1.22 physiological function UDP-glucose dehydrogenase Ugd2 is involved in building capsular polysaccharides K20 and K21. The K20 and K21 capsular polysaccharides include GlcpA produced by Ugd2 and D-galactose with an (R)-configured 4,6-pyruvic acid acetal added by Prt2. The first sugar in the tetrasaccharide K units is 2-acetamido-4-amino-2,4,6-trideoxy-D-glucose (D-QuipNAc4N) that carries a 4-N-[(S)-3-hydroxybutanoyl] group in some K units and a 4-N-acetyl group in the others 761217 1.1.1.22 physiological function UGDH is essential in the proteoglycan synthesis in articular chondrocytes, overview -, 739967 1.1.1.22 physiological function UGDH is essential in the proteoglycan synthesis in articular chondrocytes, overview. UDP-glucuronic acid is a key precursor for the synthesis of the glycosaminoglycan chain in proteoglycans 739967 1.1.1.22 physiological function UGDH oxidizes UDP-glucose to UDP-glucuronate, an essential precursor for production of hyaluronan, proteoglycans, and xenobiotic glucuronides. High levels of hyaluronan turnover in prostate cancer are correlated with aggressive progression. UGDH expression is high in the normal prostate even though hyaluronan accumulation is virtually undetectable. The enzyme's common role in the prostate may be to provide precursors for glucuronosyltransferase enzymes, which inactivate and solubilize androgens by glucuronidation. Androgen dependence of UGDH, glucuronosyltransferase, and hyaluronan synthase expression, overview 711665