3019-74-7Relevant articles and documents
The crystal structure of human transketolase and new insights into its mode of action
Mitschke, Lars,Parthier, Christoph,Schroeder-Tittmann, Kathrin,Coy, Johannes,Luedtke, Stefan,Tittmann, Kai
, p. 31559 - 31570 (2010)
The crystal structure of human transketolase (TKT), a thiamine diphosphate (ThDP) and Ca2+-dependent enzyme that catalyzes the interketol transfer between ketoses and aldoses as part of the pentose phosphate pathway, has been determined to 1.75 A resolution. The recombinantly produced protein crystallized in space group C2 containing one monomer in the asymmetric unit. Two monomers form the homodimeric biological assembly with two identical active sites at the dimer interface. Although the protomer exhibits the typical three (α/β)-domain structure and topology reported for TKTs from other species, structural differences are observed for several loop regions and the linker that connects the PP and Pyr domain. The cofactor and substrate binding sites of human TKT bear high resemblance to those of other TKTs but also feature unique properties, including two lysines and a serine that interact with the β-phosphate of ThDP. Furthermore, Gln189 spans over the thiazolium moiety of ThDP and replaces an isoleucine found in most non-mammalian TKTs. The side chain of Gln428 forms a hydrogen bond with the 4′-amino group of ThDP and replaces a histidine that is invariant in all non-mammalian TKTs. All other amino acids involved in substrate binding and catalysis are strictly conserved. Besides a steady-state kinetic analysis, microscopic equilibria of the donor half-reaction were characterized by an NMR-based intermediate analysis. These studies reveal that formation of the central 1,2-dihydroxyethyl-ThDP carbanion-enamine intermediate is thermodynamically favored with increasing carbon chain length of the donor ketose substrate. Based on the structure of human transketolase and sequence alignments, putative functional properties of the related transketolase-like proteins TKTL1 and -2 are discussed in light of recent findings suggesting that TKTL1 plays a role in cancerogenesis.
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Wolfrom et al.
, p. 2197 (1952)
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Hough,Jones
, p. 342,345 (1953)
One-Pot Cascade Synthesis of (3S)-Hydroxyketones Catalyzed by Transketolase via Hydroxypyruvate Generated in Situ from d-Serine by d-Amino Acid Oxidase
L'enfant, Mélanie,Bruna, Felipe,Lorillière, Marion,Ocal, Nazim,Fessner, Wolf-Dieter,Pollegioni, Loredano,Charmantray, Franck,Hecquet, Laurence
, p. 2550 - 2558 (2019/04/17)
We described an efficient in situ generation of hydroxypyruvate from d-serine catalyzed by a d-amino acid oxidase from Rhodotorula gracilis. This strategy revealed an interesting alternative to the conventional chemical synthesis of hydroxypyruvate starting from toxic bromopyruvate or to the enzymatic transamination from l-serine requiring an additional substrate as amino acceptor. Hydroxypyruvate thus produced was used as donor substrate of transketolases from Escherichia coli or from Geobacillus stearothermophilus catalyzing the stereoselective formation of a carbon?carbon bond. The enzymatic cascade reaction was performed in one-pot in the presence of d-serine and appropriate aldehydes for the synthesis of valuable (3S)-hydroxyketones, which were obtained with high enantio- and diastereoselectivity and in good yield. The efficiency of the process was based on the irreversibility of both reactions allowing complete conversion of d-serine and aldehydes. (Figure presented.).
Synthesis of sedoheptulose from 2-C-(hydroxymethyl)-D-allose by molybdic acid-catalysed carbon-skeleton rearrangement
Hricoviniova-Bilikova, Zuzana,Petrus, Ladislav
, p. 31 - 36 (2007/10/03)
A new branched-chain aldose, 2-C-(hydroxymethyl)-D-allose (3), was obtained by a base-catalysed addition of 2,3:5,6-di-O-isopropylidene-β-D-allofuranose to formaldehyde followed by acid hydrolysis of the aldol product. On treatment with a catalytic amount of molybdic acid at 90°C, 3 afforded its equilibrium mixture with sedoheptulose tautomeric and anhydro forms in the ratio 12:1. Sedoheptulose in its 2,7-anhydro form, 2,7-anhydro-β-D-altro-heptulopyranose, was obtained from this mixture by treatment with 0.5 M H2SO4 and crystallisation (overall 63% yield). Copyright (C) 1999 Elsevier Science Ltd.
