Article
Biochemistry & Molecular Biology
Amanda L. Darbyshire, Kirsten R. Wolthers
Summary: In Fusobacterium nucleatum, the clustering of aromatic residues is critical for the catalytic activity of serine synthase, an enzyme involved in the biosynthesis of noncanonical amino acids. Substituting these aromatic residues affects the reaction rate and the scope of nucleophilic substrates.
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
(2023)
Article
Biochemistry & Molecular Biology
Somchart Maenpuen, Pitchayathida Mee-udorn, Chatchadaporn Pinthong, Anan Athipornchai, Kochakorn Phiwkaow, Sarayut Watchasit, Panu Pimviriyakul, Thanyada Rungrotmongkol, Ruchanok Tinikul, Ubolsree Leartsakulpanich, Penchit Chitnumsub
Summary: Mangiferin, a polyphenolic xanthone glycoside, was found to inhibit both Plasmodium falciparum and human cytosolic SHMTs through competitive inhibition against tetrahydrofolate. This discovery provides the basis for the future development of mangiferin as a potent antimalarial and anticancer drug.
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
(2023)
Article
Multidisciplinary Sciences
Justyna Piechocka, Monika Wyszczelska-Rokiel, Rafal Glowacki
Summary: This report presents a method for simultaneous determination of plasma HPPTCA and total low molecular-weight thiols content. The assay is based on HPLC-UV, involving disulfides reduction, derivatization, and sample deproteinization. The HPLC-UV assay provides a complementary tool for routine clinical analysis and facilitates further studies on the role of aminothiols and HPPTCA in living systems.
SCIENTIFIC REPORTS
(2023)
Article
Chemistry, Physical
Natalia N. Kuranova, Daria Petrova, Maksim N. Zavalishin, Aleksei N. Kiselev, George A. Gamov
Summary: Hydrazones and Schiff bases are potent metal chelators with various biological activities. This paper collects protonation constant data of these compounds and proposes a chemometric model to describe the protolytic equilibria constants.
JOURNAL OF MOLECULAR LIQUIDS
(2023)
Article
Biochemistry & Molecular Biology
Alec Millner, Logan Running, Nicole Colon-Rosa, Diana S. Aga, Jonna Frasor, G. Ekin Atilla-Gokcumen
Summary: This study identifies a novel lipid regulator involved in therapy-induced senescence and suggests that ceramide kinase could be a potential target enzyme to decrease the levels of therapy-induced senescent cells.
ACS CHEMICAL BIOLOGY
(2022)
Article
Chemistry, Physical
O. N. Krutova, A. Lytkin, V. V. Chernikov, A. V. Volkov, Yu Mokhova, P. D. Krutov
Summary: The study measured the enthalpies of dissolution of crystalline pyridoxine and pyridoxal-5'-phosphate in water and KOH aqueous solutions using a direct calorimetric method. The standard enthalpies of combustion and formation were calculated based on group systematics and the effect of primary environment for atoms were taken into account. Additionally, the standard enthalpies of formation and dissociation products in aqueous solutions were also calculated.
JOURNAL OF MOLECULAR LIQUIDS
(2021)
Review
Biochemistry & Molecular Biology
Tohru Yoshimura
Summary: Enzymology, the study of enzyme structures and reaction mechanisms, is a classical discipline that has not yet reached its full potential. This review focuses on the reaction mechanisms of pyridoxal enzymes related to D-amino acid metabolism, highlighting the significance and interest of enzymology.
BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY
(2022)
Article
Multidisciplinary Sciences
Prajakatta Mulay, Cindy Chen, Vijay Krishna
Summary: This study discovered that pyridoxal-5'-phosphate (PLP) has catalytic activity and can breakdown cysteine to produce hydrogen sulfide (H2S) in the absence of enzymes and multivalent metal ions. The reaction of PLP with cysteine forms a thiazolidine product, which can slowly decompose to produce H2S. This research provides important insights into the role of PLP in metabolic pathways.
SCIENTIFIC REPORTS
(2023)
Article
Chemistry, Physical
G. A. Gamov, A. N. Kiselev, M. N. Zavalishin, D. N. Yarullin
Summary: This paper reports on the prediction and stability study of the equilibrium and rate constants of the formation and hydrolysis reactions of hydrazones and Schiff bases derived from aldehyde species of the B6 vitamin family. It also investigates their applications in aqueous solutions at different pH values. The proposed additive model proves to be effective in considering the presence or absence of the amine or hydrazide group and five-or six-membered aromatic cycles.
JOURNAL OF MOLECULAR LIQUIDS
(2023)
Article
Biochemistry & Molecular Biology
Anna Barile, Philippa Mills, Martino L. di Salvo, Claudio Graziani, Victoria Bunik, Peter Clayton, Roberto Contestabile, Angela Tramonti
Summary: The study characterized the catalytic, allosteric, and structural properties of PNPO variants, including D33V, R161C, P213S, and E50K. D33V and E50K variants had mildly altered catalytic properties, while P213S had lower thermal stability and reduced cofactor binding capability. The R161C variant significantly decreased substrate affinity and abolished allosteric feedback inhibition.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Chemistry, Physical
Anthony Meza, Meghan E. Campbell, Anna Zmich, Sierra A. Thein, Abbigail M. Grieger, Matthew J. McGill, Patrick H. Willoughby, Andrew R. Buller
Summary: Multi-enzyme biocatalytic cascades provide a practical route for the synthesis of complex bioactive molecules. In this study, a chemoenzymatic platform was developed to convert aryl epoxides into alpha-aryl aldehydes and then further react with L-threonine to produce beta-hydroxy-alpha-amino acids. The whole-cell biocatalyst, produced through co-expression of two enzymes in E. coli, demonstrated the ability to synthesize a variety of stereopure non-standard amino acids on a gram scale.
Article
Microbiology
Tomokazu Ito, Honoka Ogawa, Hisashi Hemmi, Diana M. Downs, Tohru Yoshimura
Summary: PLPBP plays a crucial role in vitamin B-6 homeostasis. This study reveals the mechanism of intracellular accumulation of PNP due to the loss of PLPBP and suggests that disruption of PLPBP perturbs PMP homeostasis.
JOURNAL OF BACTERIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Natalia N. Kuranova, Daniil N. Yarullin, Maksim N. Zavalishin, George A. Gamov
Summary: This paper investigates the chemical reaction of gold(III) complexes with five hydrazones and confirms the formation of complexes in aqueous solutions. This contributes to further studies on the interaction between gold(III) complexes and biomacromolecules.
Article
Agriculture, Dairy & Animal Science
Rong-Ju Yang, Na Wang, Xiao Ma, Meng-Die Gong, Yi-Rong Wang, Si-Yu Meng, Zhao-Ying Liu, Qi Tang
Summary: In this study, a two-dimensional liquid chromatography-UV detector was used to establish a method for simultaneous detection of PLP, PA, and PL. The method exhibited good performance in sample processing, separation, and detection, making it suitable for applications in pharmacological, pharmaceutical, and clinical research.
Article
Nutrition & Dietetics
Lei Xu, Yu-Jing Fang, Meng-Meng Che, Alinuer Abulimiti, Chu-Yi Huang, Cai-Xia Zhang
Summary: This study investigated the relationship between vitamin B-6 and colorectal cancer risk using biomarkers PLP, PL, and PAr. The results showed that serum PLP and the sum of PLP and PL were inversely associated with colorectal cancer risk, while PAr was positively associated with colorectal cancer risk. The study suggested that vitamin B-6 may have a protective role in reducing colorectal cancer risk in the Chinese population, and that inflammation and oxidative stress may play a potential role in colorectal carcinogenesis.
Article
Biochemistry & Molecular Biology
Thitapa Thongkawphueak, Ashley J. Winter, Christopher Williams, Hannah J. Maple, Siriwat Soontaranon, Chonthicha Kaewhan, Dominic J. Campopiano, Matthew P. Crump, Pakorn Wattana-Amorn
Summary: This study presents the NMR structure analysis of the doublet ACP domains from PigH, revealing the inherent plasticity of PigH ACP(1)-ACP(2) structure with conformational exchange predominantly in the ACP2 domain. Furthermore, ensemble models obtained from SAXS data show distinct conformers, bent and extended, of both apo and holo PigH ACP(1)-ACP(2) mediated by the central linker. These results provide new insights into the behavior of the interdomain linker of multiple ACP domains in modulating protein-protein interactions, which may have implications for metabolic engineering in prodigiosin and related biosynthetic pathways.
Article
Biochemistry & Molecular Biology
Alexis J. A. Hennessy, Wenli Huang, Chloe Savary, Dominic J. Campopiano
Summary: The synthesis of amides through acid and amine coupling is common but requires more sustainable and biocatalytic methods. The study identified the potential of nitrile synthetase in amide bond formation and successfully engineered a biocatalyst without the need for coupling agents. This suggests the further development of nitrile synthetases as efficient, coupling agent-free biocatalysts for amide formation.
Article
Chemistry, Multidisciplinary
Catherine A. McKenna, Maria Stiblarikova, Irene De Silvestro, Dominic J. Campopiano, Andrew L. Lawrence
Summary: The synthesis of chiral amines is a key reaction in chemical synthesis. Researchers are striving to develop more sustainable alternatives to metal-catalyzed methods currently used in various industries. By using N-phenylputrescine as an amine donor, a broad range of synthetically useful TA biocatalysts can be utilized under various reaction conditions, demonstrating its potential in practical applications like synthesizing pharmaceuticals such as sitagliptin.
Article
Multidisciplinary Sciences
Jennifer Ross, Zak McIver, Thomas Lambert, Cecilia Piergentili, Jasmine Emma Bird, Kelly J. Gallagher, Faye L. Cruickshank, Patrick James, Efrain Zarazua-Arvizu, Louise E. Horsfall, Kevin J. Waldron, Marcus D. Wilson, C. Logan Mackay, Arnaud Basle, David J. Clarke, Jon Marles-Wright
Summary: In this study, the structural relationship between the encapsulin shell and its protein cargo was investigated using cryo-electron microscopy and hydrogen/deuterium exchange mass spectrometry. The study revealed the arrangement of encapsulated ferritin decamers within the encapsulin nanocompartment and the dynamic behavior of the encapsulin shell pore.
Article
Biochemistry & Molecular Biology
Shona M. Richardson, Peter J. Harrison, Michael A. Herrera, Menglu Wang, Rebecca Verez, Gustavo Perez Ortiz, Dominic J. Campopiano
Summary: The carbon backbone of biotin is synthesized from the C-7 diacid pimelate, and the conversion to an acyl-CoA thioester is catalyzed by an ATP-dependent pimeloyl-CoA synthetase (PCAS, encoded by BioW). This acyl-thioester is then condensed with β-alanine to form an aminoketone. The study found that the BioW-BioF fusion from Corynebacterium amycolatum accepts a wider range of substrates, suggesting it is a versatile biocatalyst.
Article
Multidisciplinary Sciences
Elsa Zacco, Owen Kantelberg, Edoardo Milanetti, Alexandros Armaos, Francesco Paolo Panei, Jenna Gregory, Kiani Jeacock, David J. Clarke, Siddharthan Chandran, Giancarlo Ruocco, Stefano Gustincich, Mathew H. Horrocks, Annalisa Pastore, Gian Gaetano Tartaglia
Summary: In this study, aptamers specific for Amyotrophic Lateral Sclerosis protein TDP-43 were successfully designed and used to track TDP-43 phase transition in vitro and in cells.
NATURE COMMUNICATIONS
(2022)
Article
Microbiology
Stacey L. Heaver, Henry H. Le, Peijun Tang, Arnaud Basle, Claudia Mirretta Barone, Dai Long Vu, Jillian L. Waters, Jon Marles-Wright, Elizabeth L. Johnson, Dominic J. Campopiano, Ruth E. Ley
Summary: This study characterizes the pathways responsible for inositol lipid production in human gut Bacteroides and explores the importance of these lipids for capsule expression, antimicrobial peptide resistance, and colonization. The authors identify the biosynthetic pathway and enzymes involved in inositol lipid synthesis, and show that loss of inositol lipid production affects bacterial fitness and symbiosis in a mouse model. They also discover a previously undescribed pathway for bacterial PI-DAG synthesis. Overall, the findings suggest that inositol sphingolipid production is widespread in host-associated Bacteroidetes and has implications for symbiotic relationships.
NATURE MICROBIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Michaelone C. Vaaltyn, Maria Mateos-Jimenez, Ronel Muller, C. Logan Mackay, Adrienne L. Edkins, David J. Clarke, Clinton G. L. Veale
Summary: Contemporary medicinal chemistry considers fragment-based drug discovery (FBDD) and inhibition of protein-protein interactions (PPI) as important means of expanding the volume of druggable chemical space. This study utilized the speed and sensitivity of nanoelectrospray (nano-ESI) native mass spectrometry to identify fragments that bind to the TPR2AB domain of HOP. The fragments were validated through biophysical assessment, demonstrating binding and inhibitory activity against the TPR2A domain and the HSP90 C-terminal domain.
Article
Neurosciences
Minee L. Choi, Alexandre Chappard, Bhanu P. Singh, Catherine Maclachlan, Margarida Rodrigues, Evgenia Fedotova, Alexey Berezhnov, Suman De, Chris Peddie, Dilan Athauda, Gurvir S. Virdi, Weijia Zhang, James R. Evans, Anna Wernick, Zeinab Shadman Zanjani, Plamena R. Angelova, Noemi Esteras, Andrey Vinikurov, Katie Morris, Kiani Jeacock, Laura Tosatto, Daniel Little, Paul Gissen, David J. Clarke, Tilo Kunath, Lucy Collinson, David Klenerman, Andrey Y. Abramov, Mathew H. Horrocks, Sonia Gandhi
Summary: This study tracked the initial self-assembly, oligomerization and structural conversion of alpha-synuclein inside neurons. Early seeding events occur on mitochondrial membranes, where oligomerization induces mitochondrial dysfunction and neuronal loss.
NATURE NEUROSCIENCE
(2022)
Article
Chemistry, Physical
Shona M. Richardson, Piera M. Marchetti, Michael A. Herrera, Dominic J. Campopiano
Summary: A unique di-domain biocatalyst (PtTamH) has been discovered, which can convert fatty acids to amines and has potential applications. Moreover, the structural organization of PtTamH has been revealed.
Article
Chemistry, Multidisciplinary
Alexandre Chappard, Craig Leighton, Rebecca S. S. Saleeb, Kiani Jeacock, Sarah R. R. Ball, Katie Morris, Owen Kantelberg, Ji-Eun Lee, Elsa Zacco, Annalisa Pastore, Margaret Sunde, David J. J. Clarke, Patrick Downey, Tilo Kunath, Mathew H. H. Horrocks
Summary: Protein misfolding and aggregation are common features of neurogenerative disorders. Single-molecule techniques have allowed the characterization of these protein aggregates, previously inaccessible with traditional methods. In this study, we employed a high affinity antibody labeled with orthogonal fluorophores, along with fast-flow microfluidics and single-molecule confocal microscopy, to specifically detect alpha-synuclein in biologically relevant samples.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Multidisciplinary Sciences
Jennifer R. Shelley, Brian J. McHugh, Jimi Wills, Julia R. Dorin, Richard Weller, David J. Clarke, Donald J. Davidson
Summary: The human skin barrier is impaired in inflammatory skin diseases, and Staphylococcus aureus contributes to further barrier impairment. Previous studies have shown that the host defence peptide HBD2 can prevent damage caused by the extracellular protease V8 secreted by S. aureus. This study examines the mechanism of HBD2-mediated barrier protection in vitro.
SCIENTIFIC REPORTS
(2023)
Article
Chemistry, Analytical
Andreas Tsiamis, Anthony Buchoux, Stephen T. Mahon, Anthony J. Walton, Stewart Smith, David J. Clarke, Adam A. Stokes
Summary: The lab-on-a-chip concept, enabled by microfluidic technology, integrates multiple discrete laboratory techniques into a miniaturised system. However, previous research has focused on developing individual elements without fully optimising and miniaturising the complete system. This paper presents a demonstrator platform that fully integrates multiple technologies into a single device, enabling breakthroughs in research by incorporating all physical requirements into one device.
Article
Chemistry, Analytical
Rhona M. Cowan, Eleanor Birch, Grace Nisbet, Chimaeze Onyeiwu, Clare Campbell, Ian Archer, Dominic J. Campopiano
Summary: This study introduces a novel method for identifying and quantifying keratinase activity, which can be used for valorising the alpha-keratin found in natural wool fibres.
ANALYTICAL METHODS
(2023)
Article
Chemistry, Multidisciplinary
Clinton G. L. Veale, Maria Mateos-Jimenez, Michaelone C. Vaaltyn, Ronel Muller, Matodzi P. Makhubu, Mahama Alhassan, Beatriz G. de la Torre, Fernando Albericio, C. Logan Mackay, Adrienne L. Edkins, David J. Clarke
Summary: This study introduces a native mass spectrometry protein-peptide model as a suitable replacement for HOP-HSP90 protein-protein interaction, leading to the identification of two new peptides capable of disrupting PPI in vitro. It demonstrates a viable alternative for screening PPI inhibitors.
CHEMICAL COMMUNICATIONS
(2021)
