Genomes and Genes
Summary: Enzymes that catalyze the epimerization of chiral centers within carbohydrates or their derivatives. EC 5.1.3.
- Zhang Y, Tao F, Du M, Ma C, Qiu J, Gu L, et al. An efficient method for N-acetyl-D-neuraminic acid production using coupled bacterial cells with a safe temperature-induced system. Appl Microbiol Biotechnol. 2010;86:481-9 pubmed publisher..Our Neu5Ac biosynthetic process is favorable compared with natural product extraction, chemical synthesis, or even many other biocatalysis processes. ..
- Zhang Q, Hrmova M, Shirley N, Lahnstein J, Fincher G. Gene expression patterns and catalytic properties of UDP-D-glucose 4-epimerases from barley (Hordeum vulgare L.). Biochem J. 2006;394:115-24 pubmed..A three-dimensional model of the HvUGE revealed that its overall structural fold is highly conserved compared with the human UGE and provides a structural rationale for its ability to bind UDP-GlcNAc. ..
- Penner J, Mantey L, Elgavish S, Ghaderi D, Cirak S, Berger M, et al. Influence of UDP-GlcNAc 2-epimerase/ManNAc kinase mutant proteins on hereditary inclusion body myopathy. Biochemistry. 2006;45:2968-77 pubmed..Otherwise, the different mutations result in different enzymatic activities but not in different disease phenotypes and, therefore, do not suggest a direct role of the enzymatic function of GNE in the disease mechanism. ..
- Krause S, Aleo A, Hinderlich S, Merlini L, Tournev I, Walter M, et al. GNE protein expression and subcellular distribution are unaltered in HIBM. Neurology. 2007;69:655-9 pubmed..For diagnostic purposes, direct genetic analysis of the GNE gene in patients with IBM will remain the mainstay and is not aided by immunohistochemistry or immunoblotting using antibodies against the GNE protein. ..
- Bonin C, Reiter W. A bifunctional epimerase-reductase acts downstream of the MUR1 gene product and completes the de novo synthesis of GDP-L-fucose in Arabidopsis. Plant J. 2000;21:445-54 pubmed..Similarly, L-ascorbate levels in GER1 antisense plants were unchanged indicating that GDP-D-mannose 3,5-epimerase is encoded by a separate gene. ..
- Ghiselli G, Agrawal A. The human D-glucuronyl C5-epimerase gene is transcriptionally activated through the beta-catenin-TCF4 pathway. Biochem J. 2005;390:493-9 pubmed..The data obtained are consistent with the idea that the beta-catenin-TCF4 transactivation pathway plays a major role in modulating GLCE expression, thus contributing to the regulation of HS biosynthesis and its structural organization. ..
- Deacon A, Ni Y, Coleman W, Ealick S. The crystal structure of ADP-L-glycero-D-mannoheptose 6-epimerase: catalysis with a twist. Structure. 2000;8:453-62 pubmed..This study should prove useful in the design of mechanistic and structure-based inhibitors of the AGME catalyzed reaction. ..
- Jakimowicz P, Freel Meyers C, Walsh C, Buttner M, Lawson D. Crystallization and preliminary X-ray studies on the putative dTDP sugar epimerase NovW from the novobiocin biosynthetic cluster of Streptomyces spheroides. Acta Crystallogr D Biol Crystallogr. 2003;59:1507-9 pubmed..NovW is involved in the biosynthesis of the aminocoumarin antibiotic novobiocin, which targets the bacterial enzyme DNA gyrase, and represents the first enzyme to be crystallized from this biosynthetic pathway. ..
- Akatsu C, Mizumoto S, Kaneiwa T, Maccarana M, Malmstrom A, Yamada S, et al. Dermatan sulfate epimerase 2 is the predominant isozyme in the formation of the chondroitin sulfate/dermatan sulfate hybrid structure in postnatal developing mouse brain. Glycobiology. 2011;21:565-74 pubmed publisher..These results suggest that the IdoA-containing structures in the developing brain are mainly produced by the actions of DS-epi2 and play crucial roles in postnatal development. ..
- Gu X, Lee S, Bar Peled M. Biosynthesis of UDP-xylose and UDP-arabinose in Sinorhizobium meliloti 1021: first characterization of a bacterial UDP-xylose synthase, and UDP-xylose 4-epimerase. Microbiology. 2011;157:260-9 pubmed publisher..Our results provide new information about the ability of rhizobia to form UDP-xylose and UDP-arabinose, which are then used for the synthesis of xylose- and arabinose-containing glycans. ..
- Zimmermann V, Hennemann H, Daussmann T, Kragl U. Modelling the reaction course of N-acetylneuraminic acid synthesis from N-acetyl-D-glucosamine--new strategies for the optimisation of neuraminic acid synthesis. Appl Microbiol Biotechnol. 2007;76:597-605 pubmed..Exemplarily, it is presented how the optimal ratio of the two enzymes in the reaction can be determined and how the composition of the reaction solution in a fed-batch reactor can be designed to meet downstream processing needs. ..
- Reiter W. Biochemical genetics of nucleotide sugar interconversion reactions. Curr Opin Plant Biol. 2008;11:236-43 pubmed publisher..In a major advance for the understanding of the synthesis of arabinosylated cell wall polysaccharides, reversibly glycosylated proteins turned out to act as mutases that interconvert the pyranose and furanose forms of UDP-L-arabinose. ..
- Ghaderi D, Strauss H, Reinke S, Cirak S, Reutter W, Lucka L, et al. Evidence for dynamic interplay of different oligomeric states of UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase by biophysical methods. J Mol Biol. 2007;369:746-58 pubmed..The presence of UDP-N-acetylglucosamine strongly favors the tetrameric state, which therefore likely represents the active state of the enzyme in cells. ..
- Merkel A, Temple G, Burkart M, Losey H, Beis K, Walsh C, et al. Purification, crystallization and preliminary structural studies of dTDP-4-keto-6-deoxy-glucose-5-epimerase (EvaD) from Amycolatopsis orientalis, the fourth enzyme in the dTDP-L-epivancosamine biosynthetic pathway. Acta Crystallogr D Biol Crystallogr. 2002;58:1226-8 pubmed..The crystals of EvaD diffract to 1.5 A and have unit-cell parameters a = 98.6, b = 72.0, c = 57.1 A with space group P2(1)2(1)2. Data to this resolution were collected at the European Synchrotron Radiation Facility. ..
- Burget E, Verma R, Mølhøj M, Reiter W. The biosynthesis of L-arabinose in plants: molecular cloning and characterization of a Golgi-localized UDP-D-xylose 4-epimerase encoded by the MUR4 gene of Arabidopsis. Plant Cell. 2003;15:523-31 pubmed..The Arabidopsis genome encodes three putative proteins with >76% sequence identity to MUR4, which may explain why mur4 plants are not entirely deficient in the de novo synthesis of UDP-L-Ara. ..
- Lee Y, Chien H, Hsu W. Production of N-acetyl-D-neuraminic acid by recombinant whole cells expressing Anabaena sp. CH1 N-acetyl-D-glucosamine 2-epimerase and Escherichia coli N-acetyl-D-neuraminic acid lyase. J Biotechnol. 2007;129:453-60 pubmed..0gNeuAcL(-1)h(-1). In this process, the expensive activator, ATP, necessary for maximal activity of GlcNAc 2-epimerase in free enzyme system can be omitted. ..
- Zhu Y, Men Y, Bai W, Li X, Zhang L, Sun Y, et al. Overexpression of D-psicose 3-epimerase from Ruminococcus sp. in Escherichia coli and its potential application in D-psicose production. Biotechnol Lett. 2012;34:1901-6 pubmed publisher..More importantly, the thermostability of the novel DPE from Ruminococcus is the strongest among all of the D-psicose and D-tagatose 3-epimerases and may be suitable for the industrial production of D-psicose from fructose...
- Maccarana M, Kalamajski S, Kongsgaard M, Magnusson S, Oldberg A, Malmstrom A. Dermatan sulfate epimerase 1-deficient mice have reduced content and changed distribution of iduronic acids in dermatan sulfate and an altered collagen structure in skin. Mol Cell Biol. 2009;29:5517-28 pubmed publisher..The altered chondroitin/dermatan sulfate chains carried by decorin in skin are likely to affect collagen fibril formation and reduce the tensile strength of DS-epi1-null skin. ..
- Reiter W, Vanzin G. Molecular genetics of nucleotide sugar interconversion pathways in plants. Plant Mol Biol. 2001;47:95-113 pubmed
- Hartmann M, Duun A, Markussen S, Grasdalen H, Valla S, Skjak Braek G. Time-resolved 1H and 13C NMR spectroscopy for detailed analyses of the Azotobacter vinelandii mannuronan C-5 epimerase reaction. Biochim Biophys Acta. 2002;1570:104-12 pubmed..The NMR results were found to be in good agreement with data obtained by a radioisotope assay based on 3H-5-labeled substrates. ..
- Valla S, Li J, Ertesvag H, Barbeyron T, Lindahl U. Hexuronyl C5-epimerases in alginate and glycosaminoglycan biosynthesis. Biochimie. 2001;83:819-30 pubmed..Seaweed alginates are widely used in industry, while heparin is well established in the clinic as an anticoagulant. ..
- Mostovich L, Prudnikova T, Kondratov A, Gubanova N, Kharchenko O, Kutsenko O, et al. The TCF4/?-catenin pathway and chromatin structure cooperate to regulate D-glucuronyl C5-epimerase expression in breast cancer. Epigenetics. 2012;7:930-9 pubmed publisher..Taken together, the results indicate that GLCE expression in breast cancer is regulated by a combination of chromatin structure and TCF4/?-catenin complex activity. ..
- Rozeboom H, Bjerkan T, Kalk K, Ertesvåg H, Holtan S, Aachmann F, et al. Structural and mutational characterization of the catalytic A-module of the mannuronan C-5-epimerase AlgE4 from Azotobacter vinelandii. J Biol Chem. 2008;283:23819-28 pubmed publisher..Site-directed mutagenesis further implicates Tyr(149), His(154), and Asp(178) as being essential for activity. Tyr(149) probably acts as the proton acceptor, whereas His(154) is the proton donor in the epimerization reaction. ..
- Eshchenko T, Rykova V, Chernakov A, Sidorov S, Grigorieva E. Expression of different proteoglycans in human breast tumors. Biochemistry (Mosc). 2007;72:1016-20 pubmed..The results suggest that changes in decorin, lumican, and syndecan-1 expression in tumor tissue could induce a distortion of proteoglycan composition and mitotic activity of cells in human breast tumor. ..
- Canals R, Jimenez N, Vilches S, Regue M, Merino S, Tomas J. Role of Gne and GalE in the virulence of Aeromonas hydrophila serotype O34. J Bacteriol. 2007;189:540-50 pubmed..hydrophila mutant strains or the complemented mutants, allowed us to confirm a clear relationship between the virulence of these strains and the presence/absence of the O34 antigen LPS. ..
- Grigorieva E, Eshchenko T, Rykova V, Chernakov A, Zabarovsky E, Sidorov S. Decreased expression of human D-glucuronyl C5-epimerase in breast cancer. Int J Cancer. 2008;122:1172-6 pubmed..These findings represent the first data about involvement of human D-glucuronyl C5-epimerase in malignant transformation. ..
- Mizukoshi E, Fushimi K, Arai K, Yamashita T, Honda M, Kaneko S. Expression of chondroitin-glucuronate C5-epimerase and cellular immune responses in patients with hepatocellular carcinoma. Liver Int. 2012;32:1516-26 pubmed publisher..Chondroitin-glucuronate C5-epimerase is a potential candidate for tumour antigen with immunogenicity and the peptides derived from this antigen could be useful in HCC immunotherapy. ..
- Morrison J, Tanner M. A two-base mechanism for Escherichia coli ADP-L-glycero-D-manno-heptose 6-epimerase. Biochemistry. 2007;46:3916-24 pubmed..This study identifies the two catalytic bases as tyrosine 140 and lysine 178. A one-step enzymatic conversion of mannose into ADP-beta-mannose is also described and used to make C-6' '-substituted derivatives of this sugar nucleotide. ..
- Smith P, Myers J, Rogers C, Zhou L, Petryniak B, Becker D, et al. Conditional control of selectin ligand expression and global fucosylation events in mice with a targeted mutation at the FX locus. J Cell Biol. 2002;158:801-15 pubmed..Conditional control of fucosylation in FX(-/-) mice identifies cellular fucosylation events as essential concomitants to fertility, early growth and development, and leukocyte adhesion...
- Mayer A, Tanner M. Intermediate release by ADP-L-glycero-D-manno-heptose 6-epimerase. Biochemistry. 2007;46:6149-55 pubmed..The corresponding phenylhydrazones were identified by mass spectrometry, and the absence of any 2H isotope in the adduct obtained from the deuterated starting compound confirmed that the oxidation had occurred at C-6''. ..
- Keating D, Willits M, Long S. A Sinorhizobium meliloti lipopolysaccharide mutant altered in cell surface sulfation. J Bacteriol. 2002;184:6681-9 pubmed..Finally, we determined that the lps-212 mutation resulted in a reduced ability to elicit the formation of plant nodules and by altered infection thread structures that aborted prematurely. ..
- Crawford B, Olson S, Esko J, Pinhal M. Cloning, Golgi localization, and enzyme activity of the full-length heparin/heparan sulfate-glucuronic acid C5-epimerase. J Biol Chem. 2001;276:21538-43 pubmed..The amino-terminally truncated epimerase does not localize to any cellular compartment, whereas the full-length enzyme is in the Golgi, where heparan sulfate synthesis is thought to occur. ..
- Watt G, Leoff C, Harper A, Bar Peled M. A bifunctional 3,5-epimerase/4-keto reductase for nucleotide-rhamnose synthesis in Arabidopsis. Plant Physiol. 2004;134:1337-46 pubmed..To our knowledge, this is the first example of a bifunctional plant enzyme involved in sugar nucleotide synthesis where a single polypeptide exhibits the same activities as two separate prokaryotic enzymes. ..
- Giraud M, Leonard G, Field R, Berlind C, Naismith J. RmlC, the third enzyme of dTDP-L-rhamnose pathway, is a new class of epimerase. Nat Struct Biol. 2000;7:398-402 pubmed..Sequence alignments of other RmlC enzymes confirm that this region is very highly conserved. The enzyme is distinct structurally from other epimerases known and thus, is the first example of a new class of carbohydrate epimerase. ..
- Wolucka B, Van Montagu M. GDP-mannose 3',5'-epimerase forms GDP-L-gulose, a putative intermediate for the de novo biosynthesis of vitamin C in plants. J Biol Chem. 2003;278:47483-90 pubmed..Exogenous L-gulose and L-gulono-1,4-lactone serve as direct precursors of l-ascorbic acid in plant cells. We propose an L-gulose pathway for the de novo biosynthesis of vitamin C in plants. ..
- Pinhal M, Smith B, Olson S, Aikawa J, Kimata K, Esko J. Enzyme interactions in heparan sulfate biosynthesis: uronosyl 5-epimerase and 2-O-sulfotransferase interact in vivo. Proc Natl Acad Sci U S A. 2001;98:12984-9 pubmed..These findings provide in vivo evidence for the formation of complexes among enzymes involved in heparan sulfate biosynthesis. The functional significance of these complexes may relate to the rapidity of heparan sulfate formation. ..
- Park D, Ryu K, Choi D, Kwak J, Park C. Characterization and role of fucose mutarotase in mammalian cells. Glycobiology. 2007;17:955-62 pubmed..The results suggest that the mammalian mutarotase is functional in facilitated incorporation of fucose through the salvage pathway. ..
- Takahashi S, Kumagai M, Shindo S, Saito K, Kawamura Y. Renin inhibits N-acetyl-D-glucosamine 2-epimerase (renin-binding protein). J Biochem. 2000;128:951-6 pubmed..These results indicate that renin is an inhibitor of GlcNAc 2-epimerase, and the renin-RnBP heterodimer HMW renin is an inactive form of both renin and GlcNAc 2-epimerase activities. ..
- Ledin J, Staatz W, Li J, Götte M, Selleck S, Kjellen L, et al. Heparan sulfate structure in mice with genetically modified heparan sulfate production. J Biol Chem. 2004;279:42732-41 pubmed..4) NDST-2, although generally expressed, does not contribute significantly to tissue-specific HS structures. 5) No change in HS structure could be detected in syndecan-1-deficient mice. ..
- Gu X, Bar Peled M. The biosynthesis of UDP-galacturonic acid in plants. Functional cloning and characterization of Arabidopsis UDP-D-glucuronic acid 4-epimerase. Plant Physiol. 2004;136:4256-64 pubmed..The availability of a functional recombinant UDP-GlcA 4-epimerase will be of considerable value for the facile generation of UDP-d-GalA in the amounts required for detailed studies of pectin biosynthesis. ..
- Lopes C, Toma L, Pinhal M, Porcionatto M, Sogayar M, Dietrich C, et al. EJ-ras oncogene transfection of endothelial cells upregulates the expression of syndecan-4 and downregulates heparan sulfate sulfotransferases and epimerase. Biochimie. 2006;88:1493-504 pubmed
- Arai A, Tanaka K, Ikeuchi T, Igarashi S, Kobayashi H, Asaka T, et al. A novel mutation in the GNE gene and a linkage disequilibrium in Japanese pedigrees. Ann Neurol. 2002;52:516-9 pubmed
- Tong Y, Tempel W, Nedyalkova L, MacKenzie F, Park H. Crystal structure of the N-acetylmannosamine kinase domain of GNE. PLoS ONE. 2009;4:e7165 pubmed publisher..Please note that a web plugin is required to access this enhanced functionality. Instructions for the installation and use of the web plugin are available in Text S1. ..
- Blume A, Weidemann W, Stelzl U, Wanker E, Lucka L, Donner P, et al. Domain-specific characteristics of the bifunctional key enzyme of sialic acid biosynthesis, UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase. Biochem J. 2004;384:599-607 pubmed..In conclusion, our results reveal that the activities, as well as the oligomeric structure, of this bifunctional enzyme seem to be organized and regulated in a complex manner. ..
- Read J, Ahmed R, Morrison J, Coleman W, Tanner M. The mechanism of the reaction catalyzed by ADP-beta-L-glycero-D-manno-heptose 6-epimerase. J Am Chem Soc. 2004;126:8878-9 pubmed..In addition, the deoxygenated analogues, 7' '-deoxy-ADP-l,d-Hep and 4' '-deoxy-ADP-l,d-Hep, were both found to serve as substrates for the enzyme, indicating that oxidation at either C-7' ' or C-4' ' is not required for catalysis. ..
- Malmstrom A, Bartolini B, Thelin M, Pacheco B, Maccarana M. Iduronic acid in chondroitin/dermatan sulfate: biosynthesis and biological function. J Histochem Cytochem. 2012;60:916-25 pubmed publisher..This short review presents the biosynthesis and functions of iduronic acid-containing structures, also as revealed by the analysis of the DS-epi1- and 2-deficient mouse models. ..
- Eisenberg I, Avidan N, Potikha T, Hochner H, Chen M, Olender T, et al. The UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase gene is mutated in recessive hereditary inclusion body myopathy. Nat Genet. 2001;29:83-7 pubmed..Our findings indicate that GNE is the gene responsible for recessive HIBM...
- Ma Y, Stern R, Scherman M, Vissa V, Yan W, Jones V, et al. Drug targeting Mycobacterium tuberculosis cell wall synthesis: genetics of dTDP-rhamnose synthetic enzymes and development of a microtiter plate-based screen for inhibitors of conversion of dTDP-glucose to dTDP-rhamnose. Antimicrob Agents Chemother. 2001;45:1407-16 pubmed..The enzyme assay was used to screen 60 Peruvian plant extracts known to inhibit the growth of M. tuberculosis in culture; two extracts were active inhibitors in the enzyme assay at concentrations of less than 2 microg/ml. ..
- Habuchi H, Habuchi O, Kimata K. Sulfation pattern in glycosaminoglycan: does it have a code?. Glycoconj J. 2004;21:47-52 pubmed..In knock-down experiments of heparan sulfate 6-O-sulfotransferase, 6-O-sulfated units in HS have been shown to act as a stimulator or suppressor according to individual GF/morphogen signaling systems. ..
- Aachmann F, Svanem B, Güntert P, Petersen S, Valla S, Wimmer R. NMR structure of the R-module: a parallel beta-roll subunit from an Azotobacter vinelandii mannuronan C-5 epimerase. J Biol Chem. 2006;281:7350-6 pubmed..Based on the structure and the electrostatic surface potential of both the A- and R-module from AlgE4, a model for the appearance of the whole protein is proposed. ..
- Maccarana M, Olander B, Malmstrom J, Tiedemann K, Aebersold R, Lindahl U, et al. Biosynthesis of dermatan sulfate: chondroitin-glucuronate C5-epimerase is identical to SART2. J Biol Chem. 2006;281:11560-8 pubmed..The functional relation between dermatan sulfate and cancer is unknown but may involve known iduronic acid-dependent interactions with growth factors, selectins, cytokines, or coagulation inhibitors. ..
- Ni Y, McPhie P, Deacon A, Ealick S, Coleman W. Evidence that NADP+ is the physiological cofactor of ADP-L-glycero-D-mannoheptose 6-epimerase. J Biol Chem. 2001;276:27329-34 pubmed..A structural comparison of ADP-hep 6-epimerase with UDP-galactose 4-epimerase, which utilizes an NAD(+) cofactor, has identified the regions of ADP-hep 6-epimerase, which defines its specificity for NADP(+). ..