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The Mechanism and Emerging Materials in Thiamine Catalysis
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The Mechanism and Emerging Materials in Thiamine Catalysis

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Biochemistry".

Deadline for manuscript submissions: closed (15 October 2023) | Viewed by 1974

Special Issue Editor

Dr. Olga N. Solovjeva

E-Mail Website
Guest Editor
Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow 119992, Russia
Interests: thiamine catalysis

Special Issue Information

Dear Colleagues,

Transketolase (TK) is a kind of enzyme that is encoded by the TKT gene. As a soluble enzyme, it occurs in the cellular and extra-cellular fluid of animals, plants, and microorganisms. In animals it is present in high amounts in adipose tissue, mammary glands, the adrenal cortex, and erythrocytes. The TK level in serum is of diagnostic interest for liver diseases and cancer, while changes in the activity of this enzyme are of interest for erythrocytes and tissues with thiamine deficiency. Its cofactor, thiamine diphosphate (ThDP), is required for processes of general metabolism across all organisms. TK is a homodimeric enzyme with the kinetic properties of half-of-the-sites reactivity, and negative cooperativity. These structural and kinetic features arise as a result of the reciprocal coupling of active sites located in the area of intersubunit contact.

Transketolase is investigated by structural and kinetic methods, as well as in modeling systems. Compared with the two-substrate reaction mode, its lower rate makes it possible to obtain reaction intermediates. The nature of the nonequivalence of transketolase active sites during keto substrate binding was also clarified, which most likely consists of switching the simultaneous binding and cleavage of substrates to their alternate binding (flip-flop mechanism). Furthermore, RNA seasonally and non-covalently bound to transketolase has been shown to be a ribozyme with triose phosphate isomerase activity.

This Special Issue welcomes all the research about mechanisms and materials used in transketolase catalysis.

Dr. Olga N. Solovjeva
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • transketolase
  • thiamine diphosphate-dependent enzymes
  • thiamine catalysis
  • mass spectrometry
  • conformational mobility of enzyme molecule

Published Papers (2 papers)

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Research

15 pages, 1402 KiB  
Article
Posttranslational Acylations of the Rat Brain Transketolase Discriminate the Enzyme Responses to Inhibitors of ThDP-Dependent Enzymes or Thiamine Transport
by Vasily A. Aleshin, Thilo Kaehne, Maria V. Maslova, Anastasia V. Graf and Victoria I. Bunik
Int. J. Mol. Sci. 2024, 25(2), 917; https://doi.org/10.3390/ijms25020917 - 11 Jan 2024
Viewed by 629
Abstract
Transketolase (TKT) is an essential thiamine diphosphate (ThDP)-dependent enzyme of the non-oxidative branch of the pentose phosphate pathway, with the glucose-6P flux through the pathway regulated in various medically important conditions. Here, we characterize the brain TKT regulation by acylation in rats with [...] Read more.
Transketolase (TKT) is an essential thiamine diphosphate (ThDP)-dependent enzyme of the non-oxidative branch of the pentose phosphate pathway, with the glucose-6P flux through the pathway regulated in various medically important conditions. Here, we characterize the brain TKT regulation by acylation in rats with perturbed thiamine-dependent metabolism, known to occur in neurodegenerative diseases. The perturbations are modeled by the administration of oxythiamine inhibiting ThDP-dependent enzymes in vivo or by reduced thiamine availability in the presence of metformin and amprolium, inhibiting intracellular thiamine transporters. Compared to control rats, chronic administration of oxythiamine does not significantly change the modification level of the two detected TKT acetylation sites (K6 and K102) but doubles malonylation of TKT K499, concomitantly decreasing 1.7-fold the level of demalonylase sirtuin 5. The inhibitors of thiamine transporters do not change average levels of TKT acylation or sirtuin 5. TKT structures indicate that the acylated residues are distant from the active sites. The acylations-perturbed electrostatic interactions may be involved in conformational shifts and/or the formation of TKT complexes with other proteins or nucleic acids. Acetylation of K102 may affect the active site entrance/exit and subunit interactions. Correlation analysis reveals that the action of oxythiamine is characterized by significant negative correlations of K499 malonylation or K6 acetylation with TKT activity, not observed upon the action of the inhibitors of thiamine transport. However, the transport inhibitors induce significant negative correlations between the TKT activity and K102 acetylation or TKT expression, absent in the oxythiamine group. Thus, perturbations in the ThDP-dependent catalysis or thiamine transport manifest in the insult-specific patterns of the brain TKT malonylation and acetylations. Full article
(This article belongs to the Special Issue The Mechanism and Emerging Materials in Thiamine Catalysis)
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16 pages, 7539 KiB  
Article
New Role of Water in Transketolase Catalysis
by Olga N. Solovjeva
Int. J. Mol. Sci. 2023, 24(3), 2068; https://doi.org/10.3390/ijms24032068 - 20 Jan 2023
Viewed by 960
Abstract
Transketolase catalyzes the interconversion of keto and aldo sugars. Its coenzyme is thiamine diphosphate. The binding of keto sugar with thiamine diphosphate is possible only after C2 deprotonation of its thiazole ring. It is believed that deprotonation occurs due to the direct transfer [...] Read more.
Transketolase catalyzes the interconversion of keto and aldo sugars. Its coenzyme is thiamine diphosphate. The binding of keto sugar with thiamine diphosphate is possible only after C2 deprotonation of its thiazole ring. It is believed that deprotonation occurs due to the direct transfer of a proton to the amino group of its aminopyrimidine ring. Using mass spectrometry, it is shown that a water molecule is directly involved in the deprotonation process. After the binding of thiamine diphosphate with transketolase and its subsequent cleavage, a thiamine diphosphate molecule is formed with a mass increased by one oxygen molecule. After fragmentation, a thiamine diphosphate molecule is formed with a mass reduced by one and two hydrogen atoms, that is, HO and H2O are split off. Based on these data, it is assumed that after the formation of holotransketolase, water is covalently bound to thiamine diphosphate, and carbanion is formed as a result of its elimination. This may be a common mechanism for other thiamine enzymes. The participation of a water molecule in the catalysis of the one-substrate transketolase reaction and a possible reason for the effect of the acceptor substrate on the affinity of the donor substrate for active sites are also shown. Full article
(This article belongs to the Special Issue The Mechanism and Emerging Materials in Thiamine Catalysis)
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