Review
Endocrinology & Metabolism
Dan Ziegler, Karlheinz Reiners, Alexander Strom, Rima Obeid
Summary: This study conducted a systematic review and meta-analysis to explore the differences in thiamine levels between individuals with and without diabetes. The results showed that individuals with diabetes had lower concentrations of thiamine markers, especially those with albuminuria. These findings suggest that individuals with diabetes may have higher thiamine requirements.
METABOLISM-CLINICAL AND EXPERIMENTAL
(2023)
Article
Biochemistry & Molecular Biology
Olga N. Solovjeva
Summary: Transketolase is an enzyme that converts keto and aldo sugars. Its coenzyme, thiamine diphosphate, can only bind with keto sugar after C2 deprotonation of its thiazole ring. Mass spectrometry has shown that a water molecule is directly involved in this deprotonation process. After the formation of holotransketolase, water is covalently bound to thiamine diphosphate, allowing for the formation of a carbanion. This mechanism may be common in other thiamine enzymes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Ewa Grabowska, Magdalena Czerniecka, Urszula Czyzewska, Aneta Zambrzycka, Zenon Lotowski, Adam Tylicki
Summary: OT and DAT are antimetabolites of thiamine. In this study, DATPP was found to be a stronger competitive inhibitor of PDHC compared to OTPP, but did not significantly impact cell growth in HeLa cell culture. The differences in effect on cell growth may be due to physicochemical properties and difficulty in DAT transport.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2021)
Article
Biochemical Research Methods
Olga N. Solovjeva
Summary: This study illustrated the differences between the first stage of one-substrate and two-substrate transketolase reactions, highlighting the transfer of glycolaldehyde from the thiazole ring to the aminopyrimidine ring as a key factor in reducing the reaction rate of one-substrate reactions. Results showed that erythrulose is formed from two glycolaldehyde molecules attached to both thiamine diphosphate rings. Kinetic characteristics were determined for the two substrates, fructose 6 phosphate and glycolaldehyde.
ANALYTICAL BIOCHEMISTRY
(2021)
Article
Biochemical Research Methods
Padmaja D. Wakchaure, Bishwajit Ganguly
Summary: Riboswitches are metabolite-sensing structures that can regulate gene expression, and the thiamine pyrophosphate (TPP) riboswitch is a new target for antibiotic development. Experimental findings show that different ligands can similarly repress gene expression while inducing conformational changes that affect binding affinity and efficacy.
JOURNAL OF MOLECULAR GRAPHICS & MODELLING
(2021)
Article
Biochemistry & Molecular Biology
Hyung Jun Kim, Yingying Li, Michael Zimmermann, Yunmi Lee, Hui Wen Lim, Alvin Swee Leong, Inhee Choi, Yoonae Ko, Sangchul Lee, Jeong Jea Seo, Mooyoung Seo, Hee Kyoung Jeon, Jonathan Cechetto, Joey Kuok Hoong Yam, Liang Yang, Uwe Sauer, Soojin Jang, Kevin Pethe
Summary: This study reveals the antibacterial potency of oxythiamine in carbapenem-resistant Pseudomonas aeruginosa by inhibiting multiple enzymes and sensitizing the bacteria to various antibiotics and non-antibiotic drugs. The findings have significant implications for the development of rational drug combinations.
CELL CHEMICAL BIOLOGY
(2022)
Article
Food Science & Technology
Chen Chen, Jiajie Yuan, Haiyan Yu, Xinman Lou, Bei Wang, Zhiyuan Xu, Huaixiang Tian
Summary: This study discovered three variants of branched-chain alpha-keto acid decarboxylase (KADC) in Lactococcus lactis strains with different abilities to produce 3-methylbutanal. The KADC-long variant was found to have activity in Escherichia coli cloning experiments. KADC-long showed efficient production of 2-methylbutanal and 3-methylbutanal under optimal conditions.
Article
Biotechnology & Applied Microbiology
Takahiro Yamauchi, Takafumi Kubodera, Daisuke Miyoshi, Naoki Sugimoto, Shuji Hirohata
Summary: The study reveals that the thiA riboswitch in Aspergillus oryzae regulates alternative mRNA splicing to reduce protein production. A new TPP-dependent artificial riboswitch was constructed based on this mechanism, which promotes gene expression unlike the wild-type riboswitch. This artificial riboswitch can be used as a practical tool for gene regulation in A. oryzae.
JOURNAL OF BIOSCIENCE AND BIOENGINEERING
(2021)
Article
Biochemistry & Molecular Biology
Mizuki Aoki, Jeffrey Vinokur, Kento Motoyama, Rino Ishikawa, Michael Collazo, Duilio Cascio, Michael R. Sawaya, Tomokazu Ito, James U. Bowie, Hisashi Hemmi
Summary: Mevalonate 3,5-bisphosphate decarboxylase is an important enzyme in the Thermoplasma-type mevalonate pathway. This study determined its crystal structure and elucidated its catalytic and regulatory mechanisms.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Multidisciplinary Sciences
Donogh Maguire, Anthony Catchpole, Owen Sheerins, Dinesh Talwar, Alana Burns, Mark Blyth, Andrew Shaw, Bryn Jones, Colin Drury, Johann Harten, Innes Smith, Donald C. McMillan
Summary: This study aimed to investigate the relationship between acute changes in the systemic inflammatory response (SIR) and thiamine and magnesium dependent enzyme activity in patients undergoing elective knee arthroplasty. The findings showed that pre-operatively TDP and magnesium concentrations were normal, but post-operatively TDP concentrations increased while magnesium concentrations decreased. Thiamine and magnesium could be potentially modifiable therapeutic targets to modulate the host inflammatory response.
SCIENTIFIC REPORTS
(2021)
Article
Biochemistry & Molecular Biology
Michael Zahn, Gerhard Konig, Huy Viet Cuong Pham, Barbara Seroka, Ryszard Lazny, Guangli Yang, Ouathek Ouerfelli, Zenon Lotowski, Thore Rohwerder
Summary: This study determined the crystal structures of Actinobacterial 2-hydroxyacyl-CoA lyase, shedding light on its substrate binding and reaction mechanism. The catalytic cycle of the enzyme was structurally portrayed, and the role of residue E493 in the catalytic process was confirmed through mutations. Water molecules were also found to potentially contribute to proton transfer. The unique feature of a large C-terminal lid domain in this enzyme restricts substrate size. Overall, these findings provide important insights for biotechnological applications.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Review
Biochemistry & Molecular Biology
Margaux Sambon, Pierre Wins, Lucien Bettendorff
Summary: Thiamine thioesters, such as benfotiamine (BFT) and dibenzoylthiamine (DBT), have shown potential benefits in treating neurodegenerative diseases with antioxidant and anti-inflammatory properties. Recent studies suggest that DBT may be even more efficient than BFT in terms of anti-inflammatory potency. These thiamine thioesters have pleiotropic properties and may lead to promising advancements in neurodegenerative, neurodevelopmental, and psychiatric conditions.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Chemistry, Medicinal
Alex H. Y. Chan, Terence C. S. Ho, Imam Fathoni, Rebecca Pope, Kevin J. Saliba, Finian J. Leeper
Summary: Thiamine is metabolized into the coenzyme thiamine diphosphate (ThDP), and interrupting its utilization leads to disease states. In this study, we report the use of a cell-permeable thiamine analogue to probe the thiamine-utilization pathway and its inhibition effect on ThDP-dependent enzymes and Plasmodium falciparum proliferation.
ACS MEDICINAL CHEMISTRY LETTERS
(2023)
Article
Biochemistry & Molecular Biology
Saad Alrashdi, Federica Casolari, Aziz Alabed, Kwaku Kyeremeh, Hai Deng
Summary: This report presents a pilot study on the biotransformation of indole-containing acyloins. The study utilizes the enzymatic combination of PfTrpB variant, LAAO, and NzsH to produce acyloins with different indole substituents. The results show that NzsH has a broad substrate profile and can be further optimized via directed evolution.
Article
Chemistry, Physical
Jon Uranga, Fabian Rabe von Pappenheim, Kai Tittmann, Ricardo A. Mata
Summary: This study investigates the activation mechanism of the ThDP cofactor in human transketolase (TKT) using electronic structure methods. The findings show that the carbene species can be accessed through a pK(a) shift induced by the electrostatics of a neighboring histidine residue. These observations highlight the potential for designing biomimetic carbene catalysts and engineering tailored enzymatic carbene reactions.
JOURNAL OF PHYSICAL CHEMISTRY B
(2023)
Article
Chemistry, Multidisciplinary
Andre A. Neves, Yelena A. Wainman, Alan Wright, Mikko I. Kettunen, Tiago B. Rodrigues, Sarah McGuire, De-En Hu, Flaviu Bulat, Simonetta Geninatti Crich, Henning Stoeckmann, Finian J. Leeper, Kevin M. Brindle
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2016)
Article
Microbiology
Miguel A. Matilla, Finian J. Leeper, George P. C. Salmond
ENVIRONMENTAL MICROBIOLOGY
(2015)
Article
Chemistry, Organic
T. Masini, B. Lacy, L. Monjas, D. Hawksley, A. R. de Voogd, B. Illarionov, A. Iqbal, F. J. Leeper, M. Fischer, M. Kontoyianni, A. K. H. Hirsch
ORGANIC & BIOMOLECULAR CHEMISTRY
(2015)
Article
Chemistry, Multidisciplinary
William J. K. Crone, Natalia M. Vior, Javier Santos-Aberturas, Lukas G. Schmitz, Finian J. Leeper, Andrew W. Truman
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2016)
Article
Chemistry, Physical
S. A. Goussous, M. T. L. Casford, A. C. Murphy, G. P. C. Salmond, F. J. Leeper, P. B. Davies
JOURNAL OF PHYSICAL CHEMISTRY B
(2017)
Article
Biotechnology & Applied Microbiology
Elena Kasparyan, Michael Richter, Carola Dresen, Lydia S. Walter, Georg Fuchs, Finian J. Leeper, Tobias Wacker, Susana L. A. Andrade, Geraldine Kolter, Martina Pohl, Michael Mueller
APPLIED MICROBIOLOGY AND BIOTECHNOLOGY
(2014)
Article
Chemistry, Organic
Amjid Iqbal, El-Habib Sahraoui, Finian J. Leeper
BEILSTEIN JOURNAL OF ORGANIC CHEMISTRY
(2014)
Article
Biochemistry & Molecular Biology
Junhong Guo, Fanglu Huang, Chuan Huang, Xiaobo Duan, Xinyun Jian, Finian Leeper, Zixin Deng, Peter F. Leadlay, Yuhui Sun
CHEMISTRY & BIOLOGY
(2014)
Article
Chemistry, Multidisciplinary
Stefan Luedtke, Piotr Neumann, Karl M. Erixon, Finian Leeper, Ronald Kluger, Ralf Ficner, Kai Tittmann
Article
Chemistry, Organic
Maryam Beigi, Sabrina Loschonsky, Patrizia Lehwald, Volker Brecht, Susana L. A. Andrade, Finian J. Leeper, Werner Hummel, Michael Mueller
ORGANIC & BIOMOLECULAR CHEMISTRY
(2013)
Article
Chemistry, Organic
Yelena A. Wainman, Andre A. Neves, Shaun Stairs, Henning Stoeckmann, Heather Ireland-Zecchini, Kevin M. Brindle, Finian J. Leeper
ORGANIC & BIOMOLECULAR CHEMISTRY
(2013)
Review
Chemistry, Organic
Finian J. Leeper, James M. Kelly
ORGANIC PREPARATIONS AND PROCEDURES INTERNATIONAL
(2013)
Article
Multidisciplinary Sciences
Cheryl A. Kreinbring, Stephen P. Remillard, Paul Hubbard, Heather R. Brodkin, Finian J. Leeper, Dan Hawksley, Elaine Y. Lai, Chandler Fulton, Gregory A. Petsko, Dagmar Ringe
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2014)
Article
Chemistry, Multidisciplinary
Laia Josa-Cullere, Yelena A. Wainman, Kevin M. Brindle, Finian J. Leeper
Article
Oncology
Flaviu Bulat, Friederike Hesse, Bala Attili, Chandra Solanki, Iosif A. Mendichovszky, Franklin Aigbirhio, Finian J. Leeper, Kevin M. Brindle, Andre A. Neves
Summary: There is a clinical demand for imaging agents that can detect tumor cell death after treatment. We present a gallium-68-labeled derivative of Synaptotagmin-I for imaging tumor cell death using PET. Ga-68-C2Am could be a valuable tool for rapidly assessing tumor responses to treatment.