Three-dimensional structure of transketolase, a thiamine diphosphate dependent enzyme, at 2.5 A resolution.

Lindqvist, Ylva; Schneider, Günter; Ermler, Ulrich; Sundström, M.

doi:10.1002/j.1460-2075.1992.tb05301.x

Cited by 349 publications

(337 citation statements)

References 24 publications

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“…The crystal structure of this enzyme has con®rmed this observation [93,111]. While the two cofactor binding sites are identical according to the crystal structure, it has been speculated that a conserved hydrogen bonding pattern between the two ThDP molecules may facilitate cooperative interactions between the two active sites in TK [111].…”

Section: Oligomeric Structurementioning

confidence: 84%

“…structures [3,30,51,93,108,111] and site-directed mutagenesis studies [18,28,171] have revealed that selected residues within the motif anchor the diphosphate group of ThDP through the divalent cation; no motif residue interacts directly with the thiazole and pyrimidine portions of the cofactor.…”

Section: Transketolase: a Thiamin Diphosphate Dependent Enzymementioning

confidence: 99%

“…The three-dimensional structures of several ThDP-dependent enzymes have been determined; these are Saccharomyces cerevisiae transketolase (TK) [93,111], Lactobacillus plantarum pyruvate oxidase (POX) [108], S. uvarum pyruvate decarboxylase (PDC) [30], S. cerevisiae PDC [3] and Pseudomonas putida benzoylformate decarboxylase (BDC) [51]. Three distinct domains can be discerned in each of these structures.…”

Section: Transketolase: a Thiamin Diphosphate Dependent Enzymementioning

confidence: 99%

“…The three-dimensional structure of the latter enzyme [93,111] has been published (PDB accession code 1TRK) and crystallographic studies on the E. coli enzyme have commenced [94]. Homologous expression systems are established for the S. cerevisiae [155] and the E. coli [60,153] enzyme.…”

Section: Sources Of Tkmentioning

confidence: 99%

“…Puri®ed holoTKs from yeasts and mammalian sources have been reported to contain one molecule of ThDP per subunit [46,56,72,81,98,116,120,158], a result which has been con®rmed, at least for the S. cerevisiae enzyme, by the crystal structure [93,111].…”

Section: Cofactor Requirementsmentioning

confidence: 99%

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Properties and functions of the thiamin diphosphate dependent enzyme transketolase

Schenk

Duggleby

Nixon

1998

The International Journal of Biochemistry & Cell Biology

225

164

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This review highlights recent research on the properties and functions of the enzyme transketolase, which requires thiamin diphosphate and a divalent metal ion for its activity. The transketolase-catalysed reaction is part of the pentose phosphate pathway, where transketolase appears to control the non-oxidative branch of this pathway, although the overall¯ux of labelled substrates remains controversial. Yeast transketolase is one of several thiamin diphosphate dependent enzymes whose three-dimensional structures have been determined. Together with mutational analysis these structural data have led to detailed understanding of thiamin diphosphate catalysed reactions. In the homodimer transketolase the two catalytic sites, where dihydroxyethyl groups are transferred from ketose donors to aldose acceptors, are formed at the interface between the two subunits, where the thiazole and pyrimidine rings of thiamin diphosphate are bound. Transketolase is ubiquitous and more than 30 full-length sequences are known. The encoded protein sequences contain two motifs of high homology; one common to all thiamin diphosphate-dependent enzymes and the other a unique transketolase motif. All characterised transketolases have similar kinetic and physical properties, but the mammalian enzymes are more selective in substrate utilisation than the nonmammalian representatives. Since products of the transketolase-catalysed reaction serve as precursors for a number of synthetic compounds this enzyme has been exploited for industrial applications. Putative mutant forms of transketolase, once believed to predispose to disease, have not stood up to scrutiny. However, a modi®cation of transketolase is a marker for Alzheimer's disease, and transketolase activity in erythrocytes is a measure of thiamin nutrition. The cornea contains a particularly high transketolase concentration, consistent with the proposal that pentose phosphate pathway activity has a role in the removal of light-generated radicals. #

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Section: Oligomeric Structurementioning

confidence: 84%

Section: Transketolase: a Thiamin Diphosphate Dependent Enzymementioning

confidence: 99%

Section: Transketolase: a Thiamin Diphosphate Dependent Enzymementioning

confidence: 99%

Section: Sources Of Tkmentioning

confidence: 99%

Section: Cofactor Requirementsmentioning

confidence: 99%

See 3 more Smart Citations

Properties and functions of the thiamin diphosphate dependent enzyme transketolase

Schenk

Duggleby

Nixon

1998

The International Journal of Biochemistry & Cell Biology

225

164

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Theoretical studies on the decarboxylation reaction in thiamin catalysis

Friedemann¹,

Breitkopf²

1996

Int. J. Quantum Chem.

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mThe conformational behavior and the stability of thiazolium and thiamin diphosphate (ThDP) adducts formed by the C2 addition of the substrates pyruvate and glyoxylate to the corresponding thiamin systems are investigated within the force-field version PIMMgO as well as the semiempirical AMI and PM3 methods. Moreover, the reaction coordinate of the decarboxylation process of the adducts with respect to the C2a -COO-bond are calculated by PM3 and AM^. The calculations on the key intermediates of the Breslow mechanism are performed in order to study the steric aspects of both substrate adducts that show a different pathway in the catalytic cycle. The alternative structural findings for the decarboxylation products are compared with first 6-31~" studies on the corresponding thiazolium model systems. Especially, the P M~ calculations show that the elimination of CO, is favored if the arrangement of the carboxylate group is nearly perpendicular to the plane of the thiazolium ring. These results support the least-motion maximum-overlap mechanism in the enzymatic decarboxylation reaction, proposed by Kluger. The most stable conformers of the ThDP adducts and its decarboxylation products are characterized by V-like structures and the formation of a significant intramolecular hydrogen bonding under participation of the 4'-aminopyrimidine ring.

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GROMOS-MD simulations on the coenzyme thiamin diphosphate in apoenzyme environment

Friedemann

Fircks

Naumann

1998

Int. J. Quant. Chem.

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ABSTRACT:Thiamin diphosphate ThDP is an essential cofactor for a number of Ž . enzymes, especially of pyruvate decarboxylase PDC which catalyzes the decarboxylation of ␣-keto acids. Recently, the crystal structure of PDC-bound ThDP has been determined. Ž . Based on these X-ray data molecular dynamics MD simulations of the isolated coenzyme as well as of ThDP in its enzymatic environment were performed, using the GROMOS87 software package. In the ThDP-apoenzyme model all significant amino acid residues with a cut-off radius less than 8.5 A from the cofactor were considered. The conformational behavior and the formation of specific structures of both ThDP and enzyme-bound ThDP were investigated in order to get hints on the activity and the mechanism of the coenzyme. Therefore, trajectories of significant structural parameters were analyzed by our graphics tool. Moreover, Ramachandran-like plots with respect to significant torsion angles were used for the illustration. Finally, MD simulations on ThDP analogs with less or none catalytic activity and apoenzyme mutants were included, in order to study the cofactor-apoenzyme binding.

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Three-dimensional structure of transketolase, a thiamine diphosphate dependent enzyme, at 2.5 A resolution.

Cited by 349 publications

References 24 publications

Properties and functions of the thiamin diphosphate dependent enzyme transketolase

Properties and functions of the thiamin diphosphate dependent enzyme transketolase

Theoretical studies on the decarboxylation reaction in thiamin catalysis

GROMOS-MD simulations on the coenzyme thiamin diphosphate in apoenzyme environment

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