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Incorporation of inosine into DNA by human polymerase eta (Polη): kinetics of nucleotide misincorporation and structural basis for the mutagenicity Biochem. J. (IF 4.1) Pub Date : 2023-09-27 Zhang, Qi, Tretyakova, Natalia
Inosine, a purine nucleoside containing the hypoxanthine (HX) nucleobase, can form in DNA via hydrolytic deamination of adenine. Due to its structural similarity to guanine and the geometry of Watson–Crick base pairs, inosine can mispair with cytosine upon catalysis by DNA polymerases, leading to AT → GC mutations. Additionally, inosine plays an essential role in purine nucleotide biosynthesis, and
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Lhs1 dependent ERAD is determined by transmembrane domain context Biochem. J. (IF 4.1) Pub Date : 2023-09-27 Sukhoplyasova, Maria, Keith, Abigail M., Perrault, Emma M., Vorndran, Hannah E., Jordahl, Alexa S., Yates, Megan E., Pastor, Ashutosh, Li, Zachary, Freaney, Michael L., Deshpande, Riddhi A., Adams, David B., Guerriero, Christopher J., Shi, Shujie, Kleyman, Thomas R., Kashlan, Ossama B., Brodsky, Jeffrey L., Buck, Teresa M.
Transmembrane proteins have unique requirements to fold and integrate into the endoplasmic reticulum (ER) membrane. Most notably, transmembrane proteins must fold in three separate environments: extracellular domains fold in the oxidizing environment of the ER lumen, transmembrane domains (TMDs) fold within the lipid bilayer, and cytosolic domains fold in the reducing environment of the cytosol. Moreover
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Chemical biology tools for protein labelling: insights into cell–cell communication Biochem. J. (IF 4.1) Pub Date : 2023-09-27 Wright, Megan H.
Multicellular organisms require carefully orchestrated communication between and within cell types and tissues, and many unicellular organisms also sense their context and environment, sometimes coordinating their responses. This review highlights contributions from chemical biology in discovering and probing mechanisms of cell–cell communication. We focus on chemical tools for labelling proteins in
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Michael D. Waterfield Biochem. J. (IF 4.1) Pub Date : 2023-09-27 Downward, Julian, Parker, Peter J., Vanhaesebroeck, Bart
Mike was born on the 14th of May 1941 in Lyndhurst, Hampshire, U.K., in the heart of the New Forest, an area of outstanding natural beauty in southern England. He was one of three children for parents Kathleen and Lesley Waterfield, spending an inquisitive childhood growing up in this idyllic setting. Mike had a formative education at Portsmouth Grammar School, where he developed a passion for chemistry
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Elevated CO2 alters photosynthesis, growth and susceptibility to powdery mildew of oak seedlings Biochem. J. (IF 4.1) Pub Date : 2023-09-13 Sanchez-Lucas, Rosa, Mayoral, Carolina, Raw, Mark, Mousouraki, Maria-Anna, Luna, Estrella
Elevated CO2 (eCO2) is a determinant factor of climate change and is known to alter plant processes such as physiology, growth and resistance to pathogens. Quercus robur, a tree species integrated in most forest regeneration strategies, shows high vulnerability to powdery mildew (PM) disease at the seedling stage. PM is present in most oak forests and it is considered a bottleneck for oak woodland
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Seasonal cold induces divergent structural/biochemical adaptations in different skeletal muscles of Columba livia: evidence for nonshivering thermogenesis in adult birds Biochem. J. (IF 4.1) Pub Date : 2023-09-13 Pani, Punyadhara, Swalsingh, Gourabamani, Pani, Sunil, Senapati, Unmod, Sahu, Bijayashree, Pati, Benudhara, Rout, Subhasmita, Bal, Naresh C.
Birds are endothermic homeotherms even though they lack the well-studied heat producing brown adipose tissue (BAT), found in several clades of eutherian mammals. Earlier studies in ducklings have demonstrated that skeletal muscle is the primary organ of nonshivering thermogenesis (NST) plausibly via futile calcium (Ca2+)-handling through ryanodine receptor (RyR) and sarco–endoplasmic reticulum Ca2+-ATPase
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Cancer-associated somatic mutations in human phosphofructokinase-1 reveal a critical electrostatic interaction for allosteric regulation of enzyme activity Biochem. J. (IF 4.1) Pub Date : 2023-09-13 Voronkova, Maria A., Hansen, Heather L., Cooper, Madison P., Miller, Jacob, Sukumar, Narayanasami, Geldenhuys, Werner J., Robart, Aaron R., Webb, Bradley A.
Metabolic reprogramming, including increased glucose uptake and lactic acid excretion, is a hallmark of cancer. The glycolytic ‘gatekeeper’ enzyme phosphofructokinase-1 (PFK1), which catalyzes the step committing glucose to breakdown, is dysregulated in cancers. While altered PFK1 activity and expression in tumors have been demonstrated, little is known about the effects of cancer-associated somatic
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RyR2 C-terminal truncating variants identified in patients with arrhythmic phenotypes exert a dominant negative effect through formation of wildtype-truncation heteromers Biochem. J. (IF 4.1) Pub Date : 2023-09-13 Tian, Shanshan, Zhong, Xiaowei, Wang, Hui, Wei, Jinhong, Guo, Wenting, Wang, Ruiwu, Paul Estillore, John, Napolitano, Carlo, Duff, Henry H., Ilhan, Erkan, Knight, Linda M., Lloyd, Michael S., Roberts, Jason D., Priori, Silvia G., Chen, S.R. Wayne
Gain-of-function missense variants in the cardiac ryanodine receptor (RyR2) are linked to catecholaminergic polymorphic ventricular tachycardia (CPVT), whereas RyR2 loss-of-function missense variants cause Ca2+ release deficiency syndrome (CRDS). Recently, truncating variants in RyR2 have also been associated with ventricular arrhythmias (VAs) and sudden cardiac death. However, there are limited insights
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An efficient triose phosphate synthesis and distribution in wheat provides tolerance to higher field temperatures Biochem. J. (IF 4.1) Pub Date : 2023-08-29 Romero-Reyes, Andrea, Hernandez-Leon, Sergio G., Leyva-Carrillo, Lilia, Yepiz-Plascencia, Gloria, Reynolds, Matthew P., Paul, Matthew J., Heuer, Sigrid, Valenzuela-Soto, Elisa M.
High temperatures in the field hinder bread wheat high-yield production, mainly because of the adverse effects of heat over photosynthesis. The Yaqui Valley, the main wheat producer region in Mexico, is a zone prone to have temperatures over 30°C. The aim of this work was to test the flag leaf photosynthetic performance in 10 bread wheat genotypes grown under high temperatures in the field. The study
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How many kinases are druggable? A review of our current understanding Biochem. J. (IF 4.1) Pub Date : 2023-08-29 Anderson, Brian, Rosston, Peter, Ong, Han Wee, Hossain, Mohammad Anwar, Davis-Gilbert, Zachary W., Drewry, David H.
There are over 500 human kinases ranging from very well-studied to almost completely ignored. Kinases are tractable and implicated in many diseases, making them ideal targets for medicinal chemistry campaigns, but is it possible to discover a drug for each individual kinase? For every human kinase, we gathered data on their citation count, availability of chemical probes, approved and investigational
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Development of an OTUD1 ubiquitin variant inhibitor Biochem. J. (IF 4.1) Pub Date : 2023-08-25 Liu, Qi, Mallette, Evan, Zheng, Hui, Zhang, Wei
OTUD1 (Ovarian tumor domain-containing deubiquitinase 1) is a member of the OTU domain-containing deubiquitinase family of enzymes involved in immunoregulation and tumorigenesis pathways. OTUD1 consists of three distinct regions: an unstructured N-terminal region, an OTU-fold catalytic domain, and a ubiquitin-interacting motif (UIM) containing region. Enhanced enzymatic activity and a strong preference
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The impact of climate change on maize chemical defenses Biochem. J. (IF 4.1) Pub Date : 2023-08-25 Yactayo-Chang, Jessica P., Block, Anna K.
Climate change is increasingly affecting agriculture, both at the levels of crops themselves, and by altering the distribution and damage caused by insect or microbial pests. As global food security depends on the reliable production of major crops such as maize (Zea mays), it is vital that appropriate steps are taken to mitigate these negative impacts. To do this a clear understanding of what the
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Single-residue mutation in protein kinase C toggles between cancer and neurodegeneration Biochem. J. (IF 4.1) Pub Date : 2023-08-25 Jones, Alexander C., Kornev, Alexandr P., Weng, Jui-Hung, Manning, Gerard, Taylor, Susan S., Newton, Alexandra C.
Conventional protein kinase C (cPKC) isozymes tune the signaling output of cells, with loss-of-function somatic mutations associated with cancer and gain-of-function germline mutations identified in neurodegeneration. PKC with impaired autoinhibition is removed from the cell by quality-control mechanisms to prevent the accumulation of aberrantly active enzyme. Here, we examine how a highly conserved
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A global view of the human post-translational modification landscape Biochem. J. (IF 4.1) Pub Date : 2023-08-23 Kitamura, Naoya, Galligan, James J.
Post-translational modifications (PTMs) provide a rapid response to stimuli, finely tuning metabolism and gene expression and maintain homeostasis. Advances in mass spectrometry over the past two decades have significantly expanded the list of known PTMs in biology and as instrumentation continues to improve, this list will surely grow. While many PTMs have been studied in detail (e.g. phosphorylation
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In search for structural targets for engineering d-amino acid transaminase: modulation of pH optimum and substrate specificity Biochem. J. (IF 4.1) Pub Date : 2023-08-23 Shilova, Sofia A., Matyuta, Ilya O., Khrenova, Maria G., Nikolaeva, Alena Y., Klyachko, Natalia L., Minyaev, Mikhail E., Khomutov, Alex R., Boyko, Konstantin M., Popov, Vladimir O., Bezsudnova, Ekaterina Yu.
The development of biocatalysts requires reorganization of the enzyme's active site to facilitate the productive binding of the target substrate and improve turnover number at desired conditions. Pyridoxal-5′-phosphate (PLP) - dependent transaminases are highly efficient biocatalysts for asymmetric amination of ketones and keto acids. However, transaminases, being stereoselective enzymes, have a narrow
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Are fibrinaloid microclots a cause of autoimmunity in Long Covid and other post-infection diseases? Biochem. J. (IF 4.1) Pub Date : 2023-08-16 Kell, Douglas B., Pretorius, Etheresia
It is now well established that the blood-clotting protein fibrinogen can polymerise into an anomalous form of fibrin that is amyloid in character; the resultant clots and microclots entrap many other molecules, stain with fluorogenic amyloid stains, are rather resistant to fibrinolysis, can block up microcapillaries, are implicated in a variety of diseases including Long COVID, and have been referred
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Dimerization and autophosphorylation of the MST family of kinases are controlled by the same set of residues Biochem. J. (IF 4.1) Pub Date : 2023-08-16 Weingartner, Kyler A., Tran, Thao, Tripp, Katherine W., Kavran, Jennifer M.
The Hippo pathway controls tissue growth and regulates stem cell fate through the activities of core kinase cassette that begins with the Sterile 20-like kinase MST1/2. Activation of MST1/2 relies on trans-autophosphorylation but the details of the mechanisms regulating that reaction are not fully elucidated. Proposals include dimerization as a first step and include multiple models for potential kinase-domain
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Insights into the central role of N-acetyl-glucosamine-1-phosphate uridyltransferase (GlmU) in peptidoglycan metabolism and its potential as a therapeutic target Biochem. J. (IF 4.1) Pub Date : 2023-08-16 Soni, Vijay, Rosenn, Eric H., Venkataraman, Ramya
Several decades after the discovery of the first antibiotic (penicillin) microbes have evolved novel mechanisms of resistance; endangering not only our abilities to combat future bacterial pandemics but many other clinical challenges such as acquired infections during surgeries. Antimicrobial resistance (AMR) is attributed to the mismanagement and overuse of these medications and is complicated by
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Photoaffinity labelling displacement assay using multiple recombinant protein domains Biochem. J. (IF 4.1) Pub Date : 2023-08-16 Fallon, David J., Phillipou, Alex, Schofield, Christopher J., House, David, Tomkinson, Nicholas C. O., Bush, Jacob T.
The development and optimisation of a photoaffinity labelling (PAL) displacement assay is presented, where a highly efficient PAL probe was used to report on the relative binding affinities of compounds to specific binding sites in multiple recombinant protein domains in tandem. The N- and C-terminal bromodomains of BRD4 were used as example target proteins. A test set of 264 compounds annotated with
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SUFU promotes GLI activity in a Hedgehog-independent manner in pancreatic cancer Biochem. J. (IF 4.1) Pub Date : 2023-08-16 Paradise, Brooke D., Gainullin, Vladimir G., Almada, Luciana L., Sigafoos, Ashley N., Sen, Sandhya, Vera, Renzo E., Raja Arul, Glancis Luzeena, Toruner, Murat, Pease, David R., Gonzalez, Alina L., Mentucci, Fatima M., Grasso, Daniel H., Fernandez-Zapico, Martin E.
Aberrant activation of the Hedgehog (Hh) signaling pathway, through which the GLI family of transcription factors (TF) is stimulated, is commonly observed in cancer cells. One well-established mechanism of this increased activity is through the inactivation of Suppressor of Fused (SUFU), a negative regulator of the Hh pathway. Relief from negative regulation by SUFU facilitates GLI activity and induction
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Computational design of Matrix Metalloproteinase-9 (MMP-9) resistant to auto-cleavage Biochem. J. (IF 4.1) Pub Date : 2023-07-26 Bonadio, Alessandro, Oguche, Solomon, Lavy, Tali, Kleifeld, Oded, Shifman, Julia
Matrix metalloproteinase-9 (MMP-9) is an endopeptidase that remodels the extracellular matrix. MMP-9 has been implicated in several diseases including neurodegeneration, arthritis, cardiovascular diseases, fibrosis and several types of cancer, resulting in a high demand for MMP-9 inhibitors for therapeutic purposes. For such drug design efforts, large amounts of MMP-9 are required. Yet, the catalytic
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Structural and functional characterization of a mycobacterial methylenetetrahydrofolate reductase utilizing NADH as the exclusive cofactor Biochem. J. (IF 4.1) Pub Date : 2023-07-26 Li, Jiacong, Yang, Mingxia, Li, Weijia, Lu, Chujie, Feng, Deyu, Shang, Zhuo, Wang, Chengyuan, Lin, Wei
5,10-Methylenetetraydrofolate reductase (MTHFR) is a key enzyme in folate metabolism. MSMEG_6649, a non-canonical MTHFR from Mycobacterium smegmatis, was previously reported as a monomeric protein lacking the flavin coenzyme. However, the structural basis for its unique flavin-independent catalytic mechanism remains poorly understood. Here, we determined the crystal structures of apo MTHFR MSMEG_6649
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RhoGAP6 interacts with COPI to regulate protein transport Biochem. J. (IF 4.1) Pub Date : 2023-07-26 O'Donoghue, Lorna, Comer, Shane P., Hiebner, Dishon W., Schoen, Ingmar, von Kriegsheim, Alex, Smolenski, Albert
RhoGAP6 is the most highly expressed GTPase-activating protein (GAP) in platelets specific for RhoA. Structurally RhoGAP6 contains a central catalytic GAP domain surrounded by large, disordered N- and C-termini of unknown function. Sequence analysis revealed three conserved consecutive overlapping di-tryptophan motifs close to the RhoGAP6 C-terminus which were predicted to bind to the mu homology domain
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Outer membrane translocation of pyocins via the copper regulated TonB-dependent transporter CrtA Biochem. J. (IF 4.1) Pub Date : 2023-07-26 Premsuriya, Jiraphan, Mosbahi, Khedidja, Atanaskovic, Iva, Kleanthous, Colin, Walker, Daniel
Pseudomonas aeruginosa is a common cause of serious hospital-acquired infections, the leading proven cause of mortality in people with cystic fibrosis and is associated with high levels of antimicrobial resistance. Pyocins are narrow-spectrum protein antibiotics produced by P. aeruginosa that kill strains of the same species and have the potential to be developed as therapeutics targeting multi-drug
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Inherited disease-linked arginine76/75 mutants in Cx50 and Cx45 showed impaired homotypic and heterotypic gap junction function, but not Cx43 Biochem. J. (IF 4.1) Pub Date : 2023-07-26 Li, Tianhe, Chen, Honghong, Li, Xiaole, Stathopulos, Peter B., Bai, Donglin
Connexins form intercellular communication channels, known as gap junctions (GJs), in many tissues/organs. Mutations in connexin genes are found to be linked to various inherited diseases, but the mechanisms are not fully clear. The Arg76 (R76) in Cx50 is fully conserved across the entire connexin family and is a hotspot for five connexin-linked inherited diseases, including Cx50 and Cx46-linked congenital
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Polypharmacological repurposing approach identifies approved drugs as potential inhibitors of Mycobacterium tuberculosis Biochem. J. (IF 4.1) Pub Date : 2023-07-26 Singh, Jasdeep, Quadir, Neha, Vashishtha, Shubham, Chakraborty, Ankan, Alam, Anwar, Kundu, Bishwajit, Ahmad, Uzair, Sundar, Durai, Ehtesham, Nasreen Z., Hasnain, Seyed E.
Mycobacterium tuberculosis (M. tb), the causative pathogen of tuberculosis (TB) remains the leading cause of death from single infectious agent. Furthermore, its evolution to multi-drug resistant (MDR) and extremely drug-resistant (XDR) strains necessitate de novo identification of drug-targets/candidates or to repurpose existing drugs against known targets through drug repurposing. Repurposing of
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Short- and long-term warming events on photosynthetic physiology, growth, and yields of field grown crops Biochem. J. (IF 4.1) Pub Date : 2023-07-12 Bernacchi, Carl J., Ruiz-Vera, Ursula M., Siebers, Matthew H., DeLucia, Nicholas J., Ort, Donald R.
Global temperatures are rising from increasing concentrations of greenhouse gases in the atmosphere associated with anthropogenic activities. Global warming includes a warmer shift in mean temperatures as well as increases in the probability of extreme heating events, termed heat waves. Despite the ability of plants to cope with temporal variations in temperature, global warming is increasingly presenting
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Calcium signalling components underlying NPK homeostasis: potential avenues for exploration Biochem. J. (IF 4.1) Pub Date : 2023-07-12 Pahuja, Sonam, Bheri, Malathi, Bisht, Diksha, Pandey, Girdhar K.
Plants require the major macronutrients, nitrogen (N), phosphorus (P) and potassium (K) for normal growth and development. Their deficiency in soil directly affects vital cellular processes, particularly root growth and architecture. Their perception, uptake and assimilation are regulated by complex signalling pathways. To overcome nutrient deficiencies, plants have developed certain response mechanisms
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Respiratory epithelial cell types, states and fates in the era of single-cell RNA-sequencing Biochem. J. (IF 4.1) Pub Date : 2023-07-12 Dudchenko, Oleksandr, Ordovas-Montanes, Jose, Bingle, Colin D.
Standalone and consortia-led single-cell atlases of healthy and diseased human airways generated with single-cell RNA-sequencing (scRNA-seq) have ushered in a new era in respiratory research. Numerous discoveries, including the pulmonary ionocyte, potentially novel cell fates, and a diversity of cell states among common and rare epithelial cell types have highlighted the extent of cellular heterogeneity
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WHIRLY proteins maintain seed longevity by effects on seed oxygen signalling during imbibition Biochem. J. (IF 4.1) Pub Date : 2023-07-12 Taylor, Rachel E., Waterworth, Wanda, West, Christopher E, Foyer, Christine H.
The WHIRLY (WHY) family of DNA/RNA binding proteins fulfil multiple but poorly characterised functions in plants. We analysed WHY protein functions in the Arabidopsis Atwhy1, Atwhy3, Atwhy1why3 single and double mutants and wild type controls. The Atwhy3 and Atwhy1why3 double mutants showed a significant delay in flowering, having more siliques per plant but with fewer seeds per silique than the wild
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The N-coil and the globular N-terminal domain of plant ARGONAUTE1 are interaction hubs for regulatory factors Biochem. J. (IF 4.1) Pub Date : 2023-07-12 Bressendorff, Simon, Kausika, Swathi, Sjøgaard, Ida Marie Zobbe, Oksbjerg, Emilie Duus, Michels, Alec, Poulsen, Christian, Brodersen, Peter
The effector complex of RNA interference (RNAi) contains at its core an ARGONAUTE (AGO) protein bound to a small guide RNA. AGO proteins adopt a two-lobed structure in which the N-terminal (N) and Piwi-Argonaute-Zwille (PAZ) domains make up one lobe, while the middle (MID) and Piwi domains make up the other. Specific biochemical functions of PAZ, MID and Piwi domains of eukaryotic AGO proteins have
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A curated list of targeted optimized promiscuous ketoreductases (TOP-K) Biochem. J. (IF 4.1) Pub Date : 2023-07-12 Shanbhag, Anirudh P., Rajagopal, Sreenath, Ghatak, Arindam, Katagihallimath, Nainesh, Subramanian, Ramaswamy, Datta, Santanu
Enzymes are either specific or promiscuous catalysts in nature. The latter is portrayed by protein families like CYP450Es, Aldo-ketoreductases and short/medium-chain dehydrogenases which participate in detoxification or secondary metabolite production. However, enzymes are evolutionarily ‘blind’ to an ever-increasing synthetic substrate library. Industries and laboratories have circumvented this by
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Shaping mitochondria through fed–fast and circadian cycles Biochem. J. (IF 4.1) Pub Date : 2023-07-12 Khatri, Subhash, Kazi, Rubina, Kolthur-Seetharam, Ullas
Energy and metabolic homeostasis at the level of the whole body are dictated by the balance between nutrient intake/utilization, bioenergetic potential, and energy expenditure, which are tightly coupled with fed/fast cycles and circadian oscillation. Emerging literature has highlighted the importance of each of these mechanisms that are essential to maintain physiological homeostasis. Lifestyle changes
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Unlocking the secrets of the microbiome: exploring the dynamic microbial interplay with humans through metabolomics and their manipulation for synthetic biology applications Biochem. J. (IF 4.1) Pub Date : 2023-06-28 Muhamadali, Howbeer, Winder, Catherine L., Dunn, Warwick B., Goodacre, Royston
Metabolomics is a powerful research discovery tool with the potential to measure hundreds to low thousands of metabolites. In this review, we discuss the application of GC–MS and LC–MS in discovery-based metabolomics research, we define metabolomics workflows and we highlight considerations that need to be addressed in order to generate robust and reproducible data. We stress that metabolomics is now
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The acyl carrier proteins of lipid synthesis are busy having other affairs Biochem. J. (IF 4.1) Pub Date : 2023-06-28 Cronan, John E.
This is a review of the acyl carrier proteins (ACPs) of type II fatty acid synthesis in bacteria and mitochondria, their structures and protein interactions. Type II fatty acid synthesis in bacteria (Prog. Lipid Res. (2013) 52, 249–276; Biochim. Biophys. Acta (1996) 1302, 1–16; Annu. Rev. Biochem. (2005) 74, 791–831) and in the mitochondria of yeast and mammals (Biochim. Biophys. Acta Mol. Cell. Res
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Classification of Cushing's syndrome PKAc mutants based upon their ability to bind PKI Biochem. J. (IF 4.1) Pub Date : 2023-06-28 Omar, Mitchell H., Kihiu, Maryanne, Byrne, Dominic P., Lee, Kyung-Soon, Lakey, Tyler M., Butcher, Erik, Eyers, Patrick A., Scott, John D.
Cushing's syndrome is an endocrine disorder caused by excess production of the stress hormone cortisol. Precision medicine strategies have identified single allele mutations within the PRKACA gene that drive adrenal Cushing's syndrome. These mutations promote perturbations in the catalytic core of protein kinase A (PKAc) that impair autoinhibition by regulatory subunits and compartmentalization via
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Paradigms of receptor kinase signaling in plants Biochem. J. (IF 4.1) Pub Date : 2023-06-28 Bender, Kyle W., Zipfel, Cyril
Plant receptor kinases (RKs) function as key plasma-membrane localized receptors in the perception of molecular ligands regulating development and environmental response. Through the perception of diverse ligands, RKs regulate various aspects throughout the plant life cycle from fertilization to seed set. Thirty years of research on plant RKs has generated a wealth of knowledge on how RKs perceive
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Key allosteric and active site residues of SARS-CoV-2 3CLpro are promising drug targets Biochem. J. (IF 4.1) Pub Date : 2023-06-15 Al Adem, Kenana, Ferreira, Juliana C., Fadl, Samar, Mustafa, Morad, Rabeh, Wael M.
The main protease of SARS-CoV-2, 3-chymotrypsin-like protease (3CLpro), is a prominent target for antiviral development due to its essential role in the viral life cycle. Research has largely focused on competitive inhibitors of 3CLpro that target the active site. However, allosteric sites distal to the peptide substrate-binding region are also potential targets for the design of reversible noncompetitive
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Capturing the domain crosstalk in full length LRRK2 and LRRK2RCKW Biochem. J. (IF 4.1) Pub Date : 2023-06-15 Störmer, Eliza, Weng, Jui-Hung, Wu, Jian, Bertinetti, Daniela, Kaila Sharma, Pallavi, Ma, Wen, Herberg, Friedrich W., Taylor, Susan S.
LRR-kinase 2 (LRRK2) is a multi-domain protein with three catalytically inert N-terminal domains (NtDs) and four C-terminal domains, including a kinase and a GTPase domain. LRRK2 mutations are linked to Parkinson's Disease (PD). Recent structures of LRRK2RCKW and a full-length inactive LRRK2 (fl-LRRK2INACT) monomer revealed that the kinase domain drives LRRK2 activation. The LRR domain and also an
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Mitochondrial metabolism and dynamics in pancreatic beta cell glucose sensing Biochem. J. (IF 4.1) Pub Date : 2023-06-15 Rutter, Guy A., Sidarala, Vaibhav, Kaufman, Brett A., Soleimanpour, Scott A.
Glucose-regulated insulin secretion becomes defective in all forms of diabetes. The signaling mechanisms through which the sugar acts on the ensemble of beta cells within the islet remain a vigorous area of research after more than 60 years. Here, we focus firstly on the role that the privileged oxidative metabolism of glucose plays in glucose detection, discussing the importance of ‘disallowing' in
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Root system growth and development responses to elevated CO2: underlying signalling mechanisms and role in improving plant CO2 capture and soil C storage Biochem. J. (IF 4.1) Pub Date : 2023-06-15 Bach, Liên, Gojon, Alain
Carbon storage in soils is one of the most promising strategies for mitigating greenhouse gas emissions and the associated climate change. In this context, how plant root systems respond to the elevation of the atmospheric CO2 concentration is of crucial importance because these organs are the main source of C input into the soils. It is expected that root growth will be stimulated by elevated CO2
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Correction: Novel insights into the recognition of acetylated histone H4 tail by the TRIM24 PHD-Bromo module Biochem. J. (IF 4.1) Pub Date : 2023-05-31 Bardhan, Ishita, Barman, Soumen, Roy, Anirban, Sudhamalla, Babu
Bardhan, I., Barman, S., Roy, A., and Sudhamalla, B. (2023) Novel insights into the recognition of acetylated histone H4 tail by the TRIM24 PHD-Bromo module. Biochem. J.480 (9): 629–647. doi: https://doi.org/10.1042/BCJ20230011Due to an error in the production process, Table 1 was omitted from the published article. The complete Table 1 is presented here. Portland Press apologises for the error.
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The WW domain of IQGAP1 binds directly to the p110α catalytic subunit of PI 3-kinase Biochem. J. (IF 4.1) Pub Date : 2023-05-31 Bardwell, A. Jane, Paul, Madhuri, Yoneda, Kiku C., Andrade-Ludeña, María D., Nguyen, Oanh T., Fruman, David A., Bardwell, Lee
IQGAP1 is a multidomain cancer-associated protein that serves as a scaffold protein for multiple signaling pathways. Numerous binding partners have been found for the calponin homology, IQ and GAP-related domains in IQGAP1. Identification of a binding partner for its WW domain has proven elusive, however, even though a cell-penetrating peptide derived from this domain has marked anti-tumor activity
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Emerging functions of pseudoenzymes Biochem. J. (IF 4.1) Pub Date : 2023-05-31 Goldberg, Timea, Sreelatha, Anju
As sequence and structural databases grow along with powerful analysis tools, the prevalence and diversity of pseudoenzymes have become increasingly evident. Pseudoenzymes are present across the tree of life in a large number of enzyme families. Pseudoenzymes are defined as proteins that lack conserved catalytic motifs based on sequence analysis. However, some pseudoenzymes may have migrated amino
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Mutations in an unrecognized internal NPT2A PDZ motif disrupt phosphate transport and cause congenital hypophosphatemia Biochem. J. (IF 4.1) Pub Date : 2023-05-17 Sneddon, W. Bruce, Friedman, Peter A., Mamonova, Tatyana
The Na+-dependent phosphate cotransporter-2A (NPT2A, SLC34A1) is a primary regulator of extracellular phosphate homeostasis. Its most prominent structural element is a carboxy-terminal PDZ ligand that binds Na+/H+ Exchanger Regulatory Factor-1 (NHERF1, SLC9A3R1). NHERF1, a multidomain PDZ protein, establishes NPT2A membrane localization and is required for hormone-inhibitable phosphate transport. NPT2A
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The VEGFR/PDGFR tyrosine kinase inhibitor, ABT-869, blocks necroptosis by targeting RIPK1 kinase Biochem. J. (IF 4.1) Pub Date : 2023-05-15 Pierotti, Catia L., Jacobsen, Annette V., Grohmann, Christoph, Dempsey, Ruby K., Etemadi, Nima, Hildebrand, Joanne M., Fitzgibbon, Cheree, Young, Samuel N., Davies, Katherine A., Kersten, Wilhelmus J. A., Silke, John, Lowes, Kym N., Jousset Sabroux, Hélène, Huang, David C. S., van Delft, Mark F., Murphy, James M., Lessene, Guillaume
Necroptosis is a mode of programmed, lytic cell death that is executed by the mixed lineage kinase domain-like (MLKL) pseudokinase following activation by the upstream kinases, receptor-interacting serine/threonine protein kinase (RIPK)-1 and RIPK3. Dysregulated necroptosis has been implicated in the pathophysiology of many human diseases, including inflammatory and degenerative conditions, infectious
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ERK1/2 inhibitors act as monovalent degraders inducing ubiquitylation and proteasome-dependent turnover of ERK2, but not ERK1 Biochem. J. (IF 4.1) Pub Date : 2023-05-15 Balmanno, Kathryn, Kidger, Andrew M., Byrne, Dominic P., Sale, Matthew J., Nassman, Nejma, Eyers, Patrick A., Cook, Simon J.
Innate or acquired resistance to small molecule BRAF or MEK1/2 inhibitors (BRAFi or MEKi) typically arises through mechanisms that sustain or reinstate ERK1/2 activation. This has led to the development of a range of ERK1/2 inhibitors (ERKi) that either inhibit kinase catalytic activity (catERKi) or additionally prevent the activating pT-E-pY dual phosphorylation of ERK1/2 by MEK1/2 (dual-mechanism
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Novel insights into the recognition of acetylated histone H4 tail by the TRIM24 PHD-Bromo module Biochem. J. (IF 4.1) Pub Date : 2023-05-15 Bardhan, Ishita, Barman, Soumen, Roy, Anirban, Sudhamalla, Babu
TRIM24 is a multi-functional chromatin reader, and it binds to the estrogen receptor to activate estrogen-dependent target genes associated with tumor development. TRIM24 is known to ubiquitinate p53 via an N-terminal RING domain and binds a specific combinatorial histone signature of H3K4me0/H3K23ac via its C-terminal plant homeodomain (PHD) and bromodomain (Bromo). Aberrant expression of TRIM24 positively
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Mutagenic incorporation of inosine into DNA via T:I mismatch formation by human DNA polymerase eta (polη) Biochem. J. (IF 4.1) Pub Date : 2023-05-15 Averill, Jameson R., Jung, Hunmin
Inosine is a key intermediate in de novo purine nucleotide biosynthesis in cells. Inosine is known to be mutagenic when it is present in DNA, in place of adenine via deamination, by facilitating the incorporation of dCTP exclusively, resulting in A:T to G:C mutation. The structural basis for the mutagenicity of inosine bypass has been reported in some DNA polymerases including human DNA polymerase
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The biochemistry and physiology of long-chain dicarboxylic acid metabolism Biochem. J. (IF 4.1) Pub Date : 2023-05-15 Ranea-Robles, Pablo, Houten, Sander M.
Mitochondrial β-oxidation is the most prominent pathway for fatty acid oxidation but alternative oxidative metabolism exists. Fatty acid ω-oxidation is one of these pathways and forms dicarboxylic acids as products. These dicarboxylic acids are metabolized through peroxisomal β-oxidation representing an alternative pathway, which could potentially limit the toxic effects of fatty acid accumulation
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Genotoxic effects of the major alkylation damage N7-methylguanine and methyl formamidopyrimidine Biochem. J. (IF 4.1) Pub Date : 2023-05-15 Schmaltz, Lillian F., Koag, Myong-Chul, Kou, Yi, Zhang, Louis, Lee, Seongmin
Various alkylating agents are known to preferentially modify guanine in DNA, resulting in the formation of N7-alkylguanine (N7-alkylG) and the imidazole ring opened alkyl-formamidopyrimidine (alkyl-FapyG) lesions. Evaluating the mutagenic effects of N7-alkylG has been challenging due to the instability of the positively charged N7-alkylG. To address this issue, we developed a 2′-fluorine-mediated transition-state
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LRRC8A is responsible for exosome biogenesis and volume regulation in colon cancer cells. Biochem. J. (IF 4.1) Pub Date : 2023-05-17 Haifeng Zhang,Shiyu Cui,Zhenghui Jing,Guodan Fu,Rong Liu,Wenbao Zhao,Liting Xu,Lei Yu,Yuhui Bai,Changsheng Lv,Min Wu,Yuan Wei,Liangming Li,Shuang Peng
Exosomes are vital mediators for intercellular communications in the tumor microenvironment to accelerate colon cancer progression. Leucine-rich repeat-containing 8A (LRRC8A), the core component of the volume-regulated anion channel, is closely associated with acquiring heterogeneity for tumor cells. However, the role of LRRC8A in the exosomes remains largely unknown. Here, we reported that LRRC8A
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Overexpression of ARM repeat/U-box containing E3 ligase, PUB2 positively regulates growth and oxidative stress response in Arabidopsis Biochem. J. (IF 4.1) Pub Date : 2023-05-15 Saini, Lokesh K., Sharma, Manisha, Ravi, Barkha, Ghosh, Soma, Pahuja, Sonam, Singh, Nidhi, Pandey, Girdhar K.
Plant growth and development are governed by selective protein synthesis and degradation. Ubiquitination mediated protein degradation is governed by activating enzyme E1 followed by conjugating enzyme E2 and E3 ligase. Plant Armadillo (ARM) repeat/U-box (PUB) protein family is one of the important classes of E3 ligase. We studied the function of AtPUB2 by loss-of-function (knockout and knock down mutants)
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Self-assembly of shell protein and native enzyme in a crowded environment leads to catalytically active phase condensates Biochem. J. (IF 4.1) Pub Date : 2023-04-26 Kumar, Gaurav, Sinha, Sharmistha
The self-assembly of bacterial microcompartments is the result of several genetic, biochemical, and physical stimuli orchestrating inside the bacterial cell. In this work, we use 1,2-propanediol utilization microcompartments as a paradigm to identify the factors that physically drive the self-assembly of MCP proteins in vitro using its major shell protein and major encapsulated enzyme. We find that
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The compleX balancing act of controlling X-chromosome dosage and how it impacts mammalian germline development. Biochem. J. (IF 4.1) Pub Date : 2023-04-26 Tom Mattimoe,Bernhard Payer
In female mammals, the two X chromosomes are subject to epigenetic gene regulation in order to balance X-linked gene dosage with autosomes and in relation to males, which have one X and one Y chromosome. This is achieved by an intricate interplay of several processes; X-chromosome inactivation and reactivation elicit global epigenetic regulation of expression from one X chromosome in a stage-specific
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Divergent contribution of the MVA and MEP pathways to the formation of polyprenols and dolichols in Arabidopsis Biochem. J. (IF 4.1) Pub Date : 2023-04-26 Lipko, Agata, Pączkowski, Cezary, Perez-Fons, Laura, Fraser, Paul D., Kania, Magdalena, Hoffman-Sommer, Marta, Danikiewicz, Witold, Rohmer, Michel, Poznanski, Jaroslaw, Swiezewska, Ewa
Isoprenoids, including dolichols (Dols) and polyprenols (Prens), are ubiquitous components of eukaryotic cells. In plant cells, there are two pathways that produce precursors utilized for isoprenoid biosynthesis: the mevalonate (MVA) pathway and the methylerythritol phosphate (MEP) pathway. In this work, the contribution of these two pathways to the biosynthesis of Prens and Dols was addressed using
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The biology and type I/III hybrid nature of type I-D CRISPR–Cas systems Biochem. J. (IF 4.1) Pub Date : 2023-04-13 McBride, Tess M., Cameron, Shaharn C., Fineran, Peter C., Fagerlund, Robert D.
Prokaryotes have adaptive defence mechanisms that protect them from mobile genetic elements and viral infection. One defence mechanism is called CRISPR–Cas (clustered regularly interspaced short palindromic repeats and CRISPR-associated proteins). There are six different types of CRISPR–Cas systems and multiple subtypes that vary in composition and mode of action. Type I and III CRISPR–Cas systems
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Correction: Cutin:cutin-acid endo-transacylase (CCT), a cuticle-remodelling enzyme activity in the plant epidermis. Biochem. J. (IF 4.1) Pub Date : 2023-04-13 Xin, Anzhou, Fei, Yue, Molnar, Attila, Fry, Stephen C.
Xin, A., Fei, Y. Molnar, A. and Fry. S.C. (2021) Cutin:cutin-acid endo-transacylase (CCT), a cuticle-remodelling enzyme activity in the plant epidermis. Biochem. J.478 (4): 777–798. https://doi.org/10.1042/BCJ20200835The authors of this article have noticed that there is an error in the ‘Methods used for supplementary data’ section of their article which they would like to correct. The final sentence
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Correction: Impact of fluoroquinolones and aminoglycosides on P. aeruginosa virulence factor production and cytotoxicity. Biochem. J. (IF 4.1) Pub Date : 2023-04-13 Foulkes, Daniel M., McLean, Keri, Sloniecka, Marta, Rustidge, Sophie, Byrne, Dominic P., Haneef, Atikah S., Winstanley, Craig, Berry, Neil, Fernig, David G., Kaye, Stephen B.
The authors of the original article “Impact of fluoroquinolones and aminoglycosides on P. aeruginosa virulence factor production and cytotoxicity” (Biochem. J. (2022) 479 (24): 2511–2527; https://doi.org/10.1042/BCJ20220527) would like to correct an error in Figure 7.The authors have identified a duplicate image which was mistakenly uploaded within Figure 7A. The moxifloxacin treatment at 6 hours is
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Genome damage accumulated in seed ageing leads to plant genome instability and growth inhibition Biochem. J. (IF 4.1) Pub Date : 2023-04-12 Waterworth, Wanda M., West, Christopher E.
Successful germination and seedling establishment are important determinants of crop yields and plant survival in natural environments. Germination potential is compromised by suboptimal environmental conditions that result in seed ageing and high levels of genome damage. However, the mutagenic and growth inhibitory potential of DNA damage accumulated in seeds on subsequent seedling growth remains