2.0 2012-05-31 14:08:11 -0600 2015-06-03 15:54:51 -0600 ECMDB06354 M2MDB000667 Deoxythymidine diphosphate-L-rhamnose Deoxythymidine diphosphate (dTDP)-L-rhamnose is the precursor of L-rhamnose, a saccharide required for the virulence of some pathogenic bacteria. In gram negative bacteria such as Salmonella enterica, Vibrio cholerae or Escherichia coli 075:K5, L-rhamnose is an important residue in the O-antigen of lipopolysaccharides, which are essential for resistance to serum killing and for colonization. dTDP-L-rhamnose is synthesized from glucose-1-phosphate and deoxythymidine triphosphate (dTTP) via a pathway involving four distinct enzymes. Whereas common sugars such as glucose, fructose and mannose are all D-configured, bacteria commonly utilize the L-configured carbohydrates in pharmacologically active compounds and in their cell-wall structures. The enzymes involved in dTDP-L-rhamnose synthesis are potential targets for the design of new therapeutic agents against bacteria. (PMID 10802738, 12773151) Deoxythymidine diphosphoric acid-L-rhamnose DTDP-6-Deoxy-L-mannose DTDP-L-Rhamnose DTDP-Rhamnose TDP-Rhamnose Thymidine diphosphate rhamnose Thymidine diphosphate-L-rhamnose Thymidine diphosphoric acid rhamnose Thymidine diphosphoric acid-L-rhamnose C16H26N2O15P2 548.3296 548.080841196 {[hydroxy({[(2R,3S,5R)-3-hydroxy-5-(5-methyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-1-yl)oxolan-2-yl]methoxy})phosphoryl]oxy}({[(3R,4R,5R,6S)-3,4,5-trihydroxy-6-methyloxan-2-yl]oxy})phosphinic acid dtdp-L-rhamnose 2147-59-3 C[C@@H]1OC(OP(O)(=O)OP(O)(=O)OC[C@H]2O[C@H](C[C@@H]2O)N2C=C(C)C(=O)NC2=O)[C@H](O)[C@H](O)[C@H]1O InChI=1S/C16H26N2O15P2/c1-6-4-18(16(24)17-14(6)23)10-3-8(19)9(31-10)5-29-34(25,26)33-35(27,28)32-15-13(22)12(21)11(20)7(2)30-15/h4,7-13,15,19-22H,3,5H2,1-2H3,(H,25,26)(H,27,28)(H,17,23,24)/t7-,8-,9+,10+,11-,12+,13+,15?/m0/s1 ZOSQFDVXNQFKBY-CZRCVJRHSA-N Solid Cytosol logp -1.09 ALOGPS logs -1.68 ALOGPS solubility 1.16e+01 g/l ALOGPS logp -2.7 ChemAxon pka_strongest_acidic 1.73 ChemAxon pka_strongest_basic -3.2 ChemAxon iupac {[hydroxy({[(2R,3S,5R)-3-hydroxy-5-(5-methyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-1-yl)oxolan-2-yl]methoxy})phosphoryl]oxy}({[(3R,4R,5R,6S)-3,4,5-trihydroxy-6-methyloxan-2-yl]oxy})phosphinic acid ChemAxon average_mass 548.3296 ChemAxon mono_mass 548.080841196 ChemAxon smiles C[C@@H]1OC(OP(O)(=O)OP(O)(=O)OC[C@H]2O[C@H](C[C@@H]2O)N2C=C(C)C(=O)NC2=O)[C@H](O)[C@H](O)[C@H]1O ChemAxon formula C16H26N2O15P2 ChemAxon inchi InChI=1S/C16H26N2O15P2/c1-6-4-18(16(24)17-14(6)23)10-3-8(19)9(31-10)5-29-34(25,26)33-35(27,28)32-15-13(22)12(21)11(20)7(2)30-15/h4,7-13,15,19-22H,3,5H2,1-2H3,(H,25,26)(H,27,28)(H,17,23,24)/t7-,8-,9+,10+,11-,12+,13+,15?/m0/s1 ChemAxon inchikey ZOSQFDVXNQFKBY-CZRCVJRHSA-N ChemAxon polar_surface_area 251.08 ChemAxon refractivity 107.76 ChemAxon polarizability 46.26 ChemAxon rotatable_bond_count 8 ChemAxon acceptor_count 12 ChemAxon donor_count 7 ChemAxon physiological_charge -2 ChemAxon formal_charge 0 ChemAxon Starch and sucrose metabolism The metabolism of starch and sucrose begins with D-fructose interacting with a D-glucose in a reversible reaction through a maltodextrin glucosidase resulting in a water molecule and a sucrose. D-fructose is phosphorylated through an ATP driven fructokinase resulting in the release of an ADP, a hydrogen ion and a Beta-D-fructofuranose 6-phosphate. This compound can also be introduced into the cytoplasm through either a mannose PTS permease or a hexose-6-phosphate:phosphate antiporter. The Beta-D-fructofuranose 6-phosphate is isomerized through a phosphoglucose isomerase resulting in a Beta-D-glucose 6-phosphate. This compound can also be incorporated by glucose PTS permease or a hexose-6-phosphate:phosphate antiporter. The beta-D-glucose 6 phosphate can also be produced by a D-glucose being phosphorylated by an ATP-driven glucokinase resulting in a ADP, a hydrogen ion and a Beta-D-glucose 6 phosphate. The beta-D-glucose can produce alpha-D-glucose-1-phosphate by two methods: 1.-Beta-D-glucose is isomerized into an alpha-D-Glucose 6-phosphate and then interacts in a reversible reaction through a phosphoglucomutase-1 resulting in a alpha-D-glucose-1-phosphate. 2.-Beta-D-glucose interacts with a putative beta-phosphoglucomutase resulting in a Beta-D-glucose 1-phosphate. Beta-D-glucose 1-phosphate can be incorporated into the cytoplasm through a glucose PTS permease. This compound is then isomerized into a Alpha-D-glucose-1-phosphate The beta-D-glucose can cycle back into a D-fructose by first interacting with D-fructose in a reversible reaction through a Polypeptide: predicted glucosyltransferase resulting in the release of a phosphate and a sucrose. The sucrose then interacts in a reversible reaction with a water molecule through a maltodextrin glucosidase resulting in a D-glucose and a D-fructose. Alpha-D-glucose-1-phosphate can produce glycogen in by two different sets of reactions: 1.-Alpha-D-glucose-1-phosphate interacts with a hydrogen ion and an ATP through a glucose-1-phosphate adenylyltransferase resulting in a pyrophosphate and an ADP-glucose. The ADP-glucose then interacts with an amylose through a glycogen synthase resulting in the release of an ADP and an Amylose. The amylose then interacts with 1,4-α-glucan branching enzyme resulting in glycogen 2.- Alpha-D-glucose-1-phosphate interacts with amylose through a maltodextrin phosphorylase resulting in a phosphate and a glycogen. Alpha-D-glucose-1-phosphate can also interacts with UDP-galactose through a galactose-1-phosphate uridylyltransferase resulting in a galactose 1-phosphate and a Uridine diphosphate glucose. The UDP-glucose then interacts with an alpha-D-glucose 6-phosphate through a trehalose-6-phosphate synthase resulting in a uridine 5'-diphosphate, a hydrogen ion and a Trehalose 6- phosphate. The latter compound can also be incorporated into the cytoplasm through a trehalose PTS permease. Trehalose interacts with a water molecule through a trehalose-6-phosphate phosphatase resulting in the release of a phosphate and an alpha,alpha-trehalose.The alpha,alpha-trehalose can also be obtained from glycogen being metabolized through a glycogen debranching enzyme resulting in a the alpha, alpha-trehalose. This compound ca then be hydrated through a cytoplasmic trehalase resulting in the release of an alpha-D-glucose and a beta-d-glucose. Glycogen is then metabolized by reacting with a phosphate through a glycogen phosphorylase resulting in a alpha-D-glucose-1-phosphate and a dextrin. The dextrin is then hydrated through a glycogen phosphorylase-limit dextrin α-1,6-glucohydrolase resulting in the release of a debranched limit dextrin and a maltotetraose. This compound can also be incorporated into the cytoplasm through a maltose ABC transporter. The maltotetraose interacts with a phosphate through a maltodextrin phosphorylase releasing a alpha-D-glucose-1-phosphate and a maltotriose. The maltotriose can also be incorporated through a maltose ABC transporter. The maltotriose can then interact with water through a maltodextrin glucosidase resulting in a D-glucose and a D-maltose. D-maltose can also be incorporated through a maltose ABC transporter The D-maltose can then interact with a maltotriose through a amylomaltase resulting in a maltotetraose and a D-glucose. The D-glucose is then phosphorylated through an ATP driven glucokinase resulting in a hydrogen ion, an ADP and a Beta-D-glucose 6-phosphate PW000941 ec00500 Metabolic Novobiocin biosynthesis ec00401 Streptomycin biosynthesis ec00521 Polyketide sugar unit biosynthesis ec00523 Metabolic pathways eco01100 dTDP-L-rhamnose biosynthesis I DTDPRHAMSYN-PWY Specdb::CMs 16117 Specdb::CMs 39007 Specdb::NmrOneD 255248 Specdb::NmrOneD 255249 Specdb::NmrOneD 255250 Specdb::NmrOneD 255251 Specdb::NmrOneD 255252 Specdb::NmrOneD 255253 Specdb::NmrOneD 255254 Specdb::NmrOneD 255255 Specdb::NmrOneD 255256 Specdb::NmrOneD 255257 Specdb::NmrOneD 255258 Specdb::NmrOneD 255259 Specdb::NmrOneD 255260 Specdb::NmrOneD 255261 Specdb::NmrOneD 255262 Specdb::NmrOneD 255263 Specdb::NmrOneD 255264 Specdb::NmrOneD 255265 Specdb::NmrOneD 255266 Specdb::NmrOneD 255267 Specdb::MsMs 26108 Specdb::MsMs 26109 Specdb::MsMs 26110 Specdb::MsMs 32666 Specdb::MsMs 32667 Specdb::MsMs 32668 HMDB06354 439975 388998 C03319 35452 DTDP-RHAMNOSE Keseler, I. M., Collado-Vides, J., Santos-Zavaleta, A., Peralta-Gil, M., Gama-Castro, S., Muniz-Rascado, L., Bonavides-Martinez, C., Paley, S., Krummenacker, M., Altman, T., Kaipa, P., Spaulding, A., Pacheco, J., Latendresse, M., Fulcher, C., Sarker, M., Shearer, A. G., Mackie, A., Paulsen, I., Gunsalus, R. P., Karp, P. D. (2011). "EcoCyc: a comprehensive database of Escherichia coli biology." Nucleic Acids Res 39:D583-D590. 21097882 Kanehisa, M., Goto, S., Sato, Y., Furumichi, M., Tanabe, M. (2012). "KEGG for integration and interpretation of large-scale molecular data sets." Nucleic Acids Res 40:D109-D114. 22080510 Giraud, M. F., Leonard, G. A., Field, R. A., Berlind, C., Naismith, J. H. (2000). "RmlC, the third enzyme of dTDP-L-rhamnose pathway, is a new class of epimerase." Nat Struct Biol 7:398-402. 10802738 Dong C, Beis K, Giraud MF, Blankenfeldt W, Allard S, Major LL, Kerr ID, Whitfield C, Naismith JH: A structural perspective on the enzymes that convert dTDP-d-glucose into dTDP-l-rhamnose. Biochem Soc Trans. 2003 Jun;31(Pt 3):532-6. 12773151 Shibaev, V. N.; Kusov, Yu. Yu.; Eliseeva, G. I.; Petrenko, V. A. Synthesis of thymidine diphosphate rhamnose analogs. Ref. Dokl. Soobshch. - Mendeleevsk. S'ezd Obshch. Prikl. Khim., 11th (1975), 6 111. CODEN: 37MOAO CAN 88:191313 AN 1978:191313 dTDP-4-dehydrorhamnose reductase P37760 RMLD_ECOLI rfbD http://ecmdb.ca/proteins/P37760.xml Lipopolysaccharide core biosynthesis protein rfaS P27126 RFAS_ECOLI rfaS http://ecmdb.ca/proteins/P27126.xml dTDP-4-Dehydro-6-deoxy-L-mannose + Hydrogen ion + NADPH <> Deoxythymidine diphosphate-L-rhamnose + NADP R02777 Deoxythymidine diphosphate-L-rhamnose + Kdo-phospho-heptosyl-phospho-heptosyl-heptosyl-kdo2-lipidA > dTDP + Hydrogen ion + inner core oligosaccharide lipid A (E coli) Deoxythymidine diphosphate-L-rhamnose + NADP <> dTDP-4-Dehydro-6-deoxy-L-mannose + NADPH + Hydrogen ion R02777 4,6-Dideoxy-4-oxo-dTDP-D-glucose + NADH + Hydrogen ion <> Deoxythymidine diphosphate-L-rhamnose + NAD DTDPRHAMSYNTHMULTI-RXN a lipopolysaccharide + Deoxythymidine diphosphate-L-rhamnose a rhamnosyl lipopolysaccharide + dTDP RXN0-5129 NADP + Deoxythymidine diphosphate-L-rhamnose <> Hydrogen ion + NADPH + dTDP-4-dehydro-6-deoxy-&beta;-L-mannose DTDPDEHYRHAMREDUCT-RXN dTDP-4-dehydro-beta-L-rhamnose + NADPH + Hydrogen ion > NADP + Deoxythymidine diphosphate-L-rhamnose PW_R006004 dTDP-4-Dehydro-6-deoxy-L-mannose + Hydrogen ion + NADPH <> Deoxythymidine diphosphate-L-rhamnose + NADP dTDP-4-Dehydro-6-deoxy-L-mannose + Hydrogen ion + NADPH <> Deoxythymidine diphosphate-L-rhamnose + NADP