UDP Galactopyranose Mutase

The position of equilibrium, as would be expected, lies strongly towards the pyranose form ([/]/[p] = 0.057), the furanose form being disfavoured by the cis interactions of hydroxyalkyl chain on C4, OH C2 and pyrophosphate on Cl. A positional isotope exchange experiment, monitored by the isotope effect 

FADH-as bound in the active site of UDP-gaiactopyianose mutase 

The effect of Tris on glycosidases is rediscovered at roughly decade intervals one of the first such reports was G. Semenza and A.-K. von Balthazar, Eur. J. Biochem. 1974, 41, 149. 

See a whole series of papers with the general title Zur Kenntniss des Siissmandelemulsins by B. Helferich and collaborators in Hoppe-Seylers Z. Physiol. Chem. in the 1960s, eg. B. Helferich and T. Kleinschmidt, Hoppe-Seylers Z. Physiol. Chem., 1968, 349, 25. 

Suominen and T. Reinikainen, eds., Trichoderma reesei Celluloses and Other Hydrolases, Akateeminen Kirjakauppa, Helsinki, 1993. 

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UDP-galactopyranose mutase from Escherichia coli Acta Cryst D55 399-402. 

Sanders DAR, Staines AG, McMahon SA, McNeil MR, Whitfield C, Naismith JH. 2001b. UDP-galactopyranose mutase has a novel structure and mechanism. Nat Struct Biol 8 858-863. 

Only two reports involving the reactivity of nonconjugated selenophenes were uncovered. Both involved the preparation of selenoether carbohydrate derivatives. The preparation of selenonium inner salt 62 was accomplished by treatment of selenoether 60 with cyclic sulfate 61 (Equation 7) <2004CAR2205>. The salt 62 was utilized as a building block for the preparation of inhibitors of UDP-galactopyranose mutase. 

Carlson EE, May JF, Kiessling LL. Chemical probes of UDP-galactopyranose mutase. Chem Biol. 2006 13 825-837. 

H. Bakker, B. Kleczka, R. Gerardy-Schahn, and F. H. Routier, Identification and partial characterization of two eukaryotic UDP-galactopyranose mutases, Biol. Chem., 386 (2005) 657-661. 

Liu reported the first chemical synthesis of uridine 5 -diphospho-P-L-ara-binofuranose (117), a possible donor of L-arabinofuranose residue. Compound (117) underwent interconversion with UDP-p-L-arabinopyranose, the likely precursor of L-arabinofuranose in vivo, when incubated with UDP-galactopyranose mutase. This result provided insights into the biogenesis of L-arabinofuranose in plants. ... 

Little is known about the L-arabinofuranosyl transfer machinery. A gene in the genome of A. thaliana has been identified as a membrane-bound arabino-furanosyl transferase by its membrane-insertion sequence and the fact that mutants in the gene led to expression of mRNA, but phenotypes that were nonetheless defective in arabinan side-chains of their pectin. Attempts to use UDP-a-L-arabinopyranose as arabinofuranose donor in crude extracts, presumably in an attempt to uncover any mutase similar to UDP galactopyranose mutase (see Section 5.12.4), merely resulted in the incorporation of pyranose units into the arabinan. However, an enzyme using this donor has been shown to add the terminal arabinopyranosyl residue to the 3-position of the terminal arabinose of the 1,5-arabininan of rhamnogalacturonan 1. [By contrast, the o-arabinofuranosyl transfer machinery that produces the... 

D-Galactofuranose residues occur in cell-wall and extracellular polysaccharides of certain bacteria, but not in mammals. The o-galactofuranose donor is UDP-galactofuranose, generated from UDP-galactopyranose by the remarkable enzyme UDP-galactopyranose mutase. Since the mutase does not occur in mammals, inhibitors are attractive potential antibacterials. The most likely mechanism involves nucleophilic displacements at the anomeric centre and so the enzyme is considered here (Figure 5.67). 

Figure 5.68 Flavin/imine mechanism of UDP galactopyranose mutase. The direction of curvature of bound FADH as shown in the X-ray crystal structure is sketched.

UDP-Gal/is produced from UDP-Gal by the enzyme UDP-galactopyranose mutase (Gif) Figure 5(b). This essential enzyme uses FADH as a cofactor and evidence has been published that a covalent FADH2-Gal intermediate is formed from the UDP-Gal substrate that undergoes pyranose/furanose equilibrium and is then reattached to UDP. Gif has been crystallized from several species including M. tuberculosis but not... 

Galactofuranose (Gal/)-containing oligosaccharides are part of the cell walls of bacteria, but are not found in humans. The first step of Gal/incorporation into oligosaccharides is catalyzed by UDP-galactopyranose mutase (UGM). UGM is an FAD-containing enzyme that catalyzes the conversion of UDP-galactopyranose (UDP-Gal/)) to UDP-Gal/(Equation (21))." " " ... 

M. McNeil, K. Duncan, Galactofuranose biosynthesis in Escherichia coli K-12 Identification and cloning of UDP-galactopyranose mutase, J. Bacteriol. 1996, 178, 1047-1052. 

Q. Zhang, H. Liu, Mechanistic investigation of UDP-galactopyranose mutase from Escherichia coli using 2- and 3-fluorinated UDP-galactofuranose as probes, J. Am. Chem. Soc. 2001, 123, 6756-6766. 

J.N. Barlow, J.S. Blanchard, Enzymatic synthesis of UDP-(3-deoxy-3-fluoro)-D-galactose and UDP-(2-deoxy-2-fluoro)-D-galactose and substrate activity with UDP-galactopyranose mutase, Carbohydr. Res. 2000, 328, 473-480. 

N. Veerapen, Y. Yuan, D.A.R. Sanders, B.M. Pinto, Synthesis of novel ammonium and selenium ions and their evaluation as inhibitors of UDP-galactopyranose mutase, Carbohydr. Res. 2004, 339,... 

M.S. Scherman, K.A. Winans, R.J. Stern, V. Jones, C.R. Bertozzi, M.R. McNeil, Drug targeting mycobacterium tuberculosis cell wall synthesis development of a microtiter plate-based screen for UDP-galactopyranose mutase and identification of an inhibitor from a uridine-based library, Antimicrob. Agents Chemother. 2003, 47, 378-382. 

M. Soltero-Higgin, E.E. Carlson, T.D. Gruber, L.L. Kiessling, A unique catalytic mechanism for UDP-galactopyranose mutase, Nat. Struct. Mol. Biol. 2004, 11, 539-543. 

M. Showalter, C.L. Griffith, T.L. Doering, V.C. Jones, M.R. McNeil, Eukaryotic UDP-galactopyranose mutase (GLF gene) in microbial and metazoal pathogens, Eukaryot. Cell... 

Soltero-Higgin, M., Carlson, E.E., Phillips, J.H., Kiessfing, L.L. 2004. Identification of inhibitors for UDP-galactopyranose mutase. Journal of the American Chemical Society 126(34) 10532-10533. 

Rate liver carbamoylphosphate synthetase I and ornithine transcarbamoyiase UDP-galactopyranose mutase... 

Selectfluor has been used for the fluorination of phosphonylated exo-glycals. Both diastereoisomers of UDP-fluoro-ejco-galactal (262) and (263) were synthesised. As expected, they displayed time-dependent inactivation of UDP-galactopyranose mutase (Scheme 105). ... 

Oppenheimer et al., 2011. Isolation and characterization of functional Leishmania major virulence factor UDP-galactopyranose mutase. Biochemical and Biophysical Research Communications, 407 552-556. 

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