Article
Endocrinology & Metabolism
Momoka Imai, Kosuke Kawaguchi, Masashi Morita, Tsuneo Imanaka, Takanori So
Summary: ABCD4, a protein belonging to the ABC protein subfamily D, plays a role in transporting cobalamin from lysosomes to the cytosol. This study revealed that TM helix 6 of ABCD4 is crucial for substrate recognition, and the charged state in the C-terminal half of TM helix 6 determines the cobalamin transport activity.
JOURNAL OF INHERITED METABOLIC DISEASE
(2023)
Article
Nutrition & Dietetics
Michinori Matsuo, Yutaka Ogata, Yoshihide Yamanashi, Tappei Takada
Summary: ATP-binding cassette protein G5 (ABCG5)/ABCG8 heterodimer exports cholesterol from cells, while Niemann-Pick C1-like 1 (NPC1L1) imports cholesterol and vitamin K. This study found that ABCG5/ABCG8 transports vitamin K-3 out of cells, and this transport is competitively inhibited by vitamin K-1. The findings suggest that ABCG5 and ABCG8 are involved in the transport of sterols and vitamin K, and ABCG5/ABCG8 and NPC1L1 might play important roles in the regulation of vitamin K absorption and excretion.
Article
Chemistry, Analytical
Huan Wang, Wencheng Mu, Siying Wang, Yuanyuan Liu, Baocheng Ran, Lin Shi, Tianfeng Ma, Yongchang Lu
Summary: In this study, F-CuNPs were synthesized using a modified liquid-phase chemical reduction method. The F-CuNPs and vitamin B2 showed possible Förster resonance energy transfer (FRET) due to spectral overlap. A FRET system between F-CuNPs and vitamin B2 was designed for the detection of vitamin B2. The system was also used for the detection of S2- based on ratiometric fluorescent probe, showing high sensitivity and selectivity.
Article
Microbiology
Zhenyao Luo, Jacqueline R. Morey, Evelyne Deplazes, Alina Motygullina, Aimee Tan, Katherine Ganio, Stephanie L. Neville, Nikolaos Eleftheriadis, Michael Isselstein, Victoria G. Pederick, James C. Paton, Thorben Cordes, Jeffrey R. Harmer, Bostjan Kobe, Christopher A. McDevitt
Summary: This study elucidates a novel mechanism for zinc binding in Streptococcus pneumoniae's AdcA protein and highlights the importance of the N-terminal domain for zinc import, as well as a conserved loop region crucial for zinc acquisition. These findings provide insights into the structural and functional basis of selective zinc uptake in prokaryotes.
Review
Biochemistry & Molecular Biology
James S. Davies, Michael J. Currie, Joshua D. Wright, Michael C. Newton-Vesty, Rachel A. North, Peter D. Mace, Jane R. Allison, Renwick C. J. Dobson
Summary: Multicomponent transporters in bacteria are crucial for the uptake of nutrients, with implications for colonization and pathogenicity in humans. Current research focuses on the membrane interactions and the roles of lipids and higher oligomers in these complex systems.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2021)
Review
Pharmacology & Pharmacy
Jing-Quan Wang, Yuqi Yang, Chao-Yun Cai, Qiu-Xu Teng, Qingbin Cui, Jun Lin, Yehuda G. Assaraf, Zhe-Sheng Chen
Summary: ABC transporters mediate the translocation of structurally and mechanistically distinct substrates against steep concentration gradients using ATP energy. The ABCC subfamily is the largest in humans, with 13 members, including 9 multidrug resistance proteins that can extrude chemotherapeutic agents from tumor cells. Additionally, MRPs are also involved in the efflux of physiologically important organic anions and are potential targets for overcoming cancer multidrug resistance.
DRUG RESISTANCE UPDATES
(2021)
Article
Microbiology
Fei Yan, Sheng Dong, Ya-Jun Liu, Xingzhe Yao, Chao Chen, Yan Xiao, Edward A. Bayer, Yuval Shoham, Chun You, Qiu Cui, Yingang Feng
Summary: This study clarifies the function and mechanism of substrate specificity of the five putative sugar transporters in Clostridium thermocellum. The results showed that transporter B is the major cellodextrin transporter, while transporter A is the major glucose transporter. The missing ATPase gene of transporter B was identified, and the correlation between transporter B and cellulosome production was revealed. Understanding the mechanism of cellodextrin utilization in C. thermocellum will facilitate the engineering of this strain for industrial applications.
Article
Biotechnology & Applied Microbiology
Hela Trigui-Lahiani, Salma Abdeljalil, Azza Hadj Sassi, Houda Skouri-Gargouri, Ali Gargouri
Summary: In this study, a gene encoding an ABC transporter was successfully cloned from P. occitanis using PCR and genomic library screening, with additional validation through whole genome sequencing. The encoded protein showed high similarity to pleiotropic drug resistance protein subfamily members, and molecular analysis revealed the presence of critical motifs. The genome-scale identification of the PoABC superfamily members characterized 58 putative proteins divided into subfamilies, with most containing transmembrane domains.
Article
Multidisciplinary Sciences
Harlan L. Pietz, Ata Abbas, Zachary Lee Johnson, Michael L. Oldham, Hiroaki Suga, Jue Chen
Summary: This study identifies a macrocyclic peptide CPI1 that inhibits the function of MRP1 and blocks substrate transport. The findings suggest that CPI1 could be a potential therapeutic candidate.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Biochemistry & Molecular Biology
Flora Szeri, Valentina Corradi, Fatemeh Niaziorimi, Sylvia Donnelly, Gwenaelle Conseil, Susan P. C. Cole, D. Peter Tieleman, Koen van de Wetering
Summary: ABCC6 inactivating mutations cause the rare hereditary mineralization disorder pseudoxanthoma elasticum. ABCC6 is proposed to be an ATP-dependent ATP efflux pump, with a potential ATP-binding site in its substrate-binding cavity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Mohammad A. Rashid, Yaping Lin-Moshier, Gihan S. Gunaratne, Sreya Subramanian, Jonathan S. Marchant, Veedamali S. Subramanian
Summary: The study identifies secretory carrier-associated membrane protein-2 (SCAMP2) as a novel accessory protein partner for the human sodium-dependent vitamin C transporter-1 (hSVCT1). Co-localization and functional studies reveal that SCAMP2 regulates ascorbic acid uptake in absorptive epithelia and during neurogenesis. Knockdown of both endogenous hSVCT1 and SCAMP2 impairs differentiation of human-induced pluripotent stem cells (hiPSCs) towards a neuronal fate.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Article
Biochemistry & Molecular Biology
James I. Mitchell-White, Thomas Stockner, Nicholas Holliday, Stephen J. Briddon, Ian D. Kerr
Summary: Members of the mammalian G subfamily of ATP-binding cassette transporters exhibit significant differences in substrate specificity, with ABCG2 playing a crucial role in multidrug resistance due to its wide substrate specificity. Analysis of conservation differences between members in a multiple sequence alignment of ABCG sequences from mammals reveals possible explanations for functional differences. Mapping sets of residues onto the 3D structure of ABCG2 illustrates a network of residues that may confer additional conformational flexibility, allowing for transport of a wider array of substrates.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Manuel Wagner, Daniel Blum, Stefanie L. Raschka, Lea-Marie Nentwig, Christoph G. W. Gertzen, Minghao Chen, Christos Gatsogiannis, Andrzej Harris, Sander H. J. Smits, Richard Wagner, Lutz Schmitt
Summary: This study demonstrates that Pdr5, as a multidrug resistance (MDR) efflux pump, not only actively transports substrates across the lipid bilayer, but also generates a proton motif force in the presence of Mg2+-ATP and substrates, thereby increasing its effectiveness.
JOURNAL OF MOLECULAR BIOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Changping Zhou, Huigang Shi, Manfeng Zhang, Lijun Zhou, Le Xiao, Shasha Feng, Wonpil Im, Min Zhou, Xinzheng Zhang, Yihua Huang
Summary: This study focuses on the structure and function of MlaFEBD in P. aeruginosa, revealing its role in PL transport. The structure shows that the MlaFEBD complex contains 12 protein molecules, and unlike canonical ABC transporters, nucleotide binding does not trigger significant conformational changes.
JOURNAL OF MOLECULAR BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Benedict-Uy Fabia, Joshua Bingwa, Jiyeon Park, Nguyen-Mihn Hieu, Jung-Hoon Ahn
Summary: Pseudomonas fluorescens, after deletion of the master regulator of flagella gene expression fleQ, produced six recombinant growth factors successfully and simplified the purification process. The strain, named P. fluorescens Delta fleQ, shows potential as an eco-friendly protein manufacturing factory with the help of a supercharging process.
Article
Genetics & Heredity
Patrick Forny, Tanja Plessl, Caroline Frei, Celine Burer, D. Sean Froese, Matthias R. Baumgartner
Summary: Pathogenic variants in MMAB lead to cblB-type methylmalonic aciduria, with p.(Arg186Trp) and p.(Arg191Trp) being the most common. The propionate incorporation ratio in fibroblasts is associated with clinical cobalamin responsiveness and disease onset time.
Article
Endocrinology & Metabolism
Ulrike Muetze, Florian Gleich, Ivo Baric, Mathias Baumgartner, Alberto Burlina, Kimberly A. Chapman, Yin-Hsiu Chien, Elisenda Cortes-Saladelafont, Corinne De Laet, Dries Dobbelaere, Francois Eysken, Matthias Gautschi, Rene Santer, Johannes Haeberle, Clara Joaquin, Daniela Karall, Martin Lindner, Allan M. Lund, Chris Muehlhausen, Elaine Murphy, Dominique Roland, Angeles Ruiz Gomez, Anastasia Skouma, Sarah C. Gruenert, Margreet Wagenmakers, Sven F. Garbade, Stefan Koelker, Nikolas Boy
Summary: This study evaluates the impact of SARS-CoV-2 infections on medical health care and disease outcome in patients with intoxication-type inherited metabolic disorders. The findings indicate that most infected individuals experienced mild symptoms and did not require hospitalization, and no complications specific to inherited metabolic disorders or COVID-19 were observed.
JOURNAL OF INHERITED METABOLIC DISEASE
(2023)
Review
Endocrinology & Metabolism
Thomas J. McCorvie, Douglas Ferreira, Wyatt W. W. Yue, D. Sean Froese
Summary: Vitamin B-12 is an essential cofactor for two human enzymes, and its metabolism involves a complex network of transporters, enzymes, and chaperones. Recent studies have provided new insights into the structure and interactions of these proteins and how they regulate the absorption, transportation, and utilization of vitamin B-12. Future research combining structural and interactome-based approaches and considering post-translational modifications holds great promise for further understanding of vitamin B-12 metabolism.
JOURNAL OF INHERITED METABOLIC DISEASE
(2023)
Article
Endocrinology & Metabolism
Patrick Forny, Friederike Hoerster, Matthias R. R. Baumgartner, Stefan Koelker, Nikolas Boy
Summary: Organic acidurias, such as GA1, MMA, and PA, have guidelines for diagnosis and management, but the development of these guidelines is hindered by limited evidence. Observational studies have contributed to improving the quality of evidence and guiding the formulation of guideline recommendations, but there are still significant gaps in evidence regarding prognosis and treatment.
JOURNAL OF INHERITED METABOLIC DISEASE
(2023)
Article
Biotechnology & Applied Microbiology
Hyobin Jeong, Karen Grimes, Kerstin K. Rauwolf, Peter-Martin Bruch, Tobias Rausch, Patrick Hasenfeld, Eva Benito, Tobias Roider, Radhakrishnan Sabarinathan, David Porubsky, Sophie A. Herbst, Busra Erarslan-Uysal, Johann-Christoph Jann, Tobias Marschall, Daniel Nowak, Jean-Pierre Bourquin, Andreas E. Kulozik, Sascha Dietrich, Beat Bornhauser, Ashley D. Sanders, Jan O. Korbel
Summary: This study introduces a computational method called scNOVA, which utilizes Strand-seq to analyze structural variations in single cells and infer gene expression. The research reveals the impact of structural variations on gene regulation and signaling pathways, and successfully applies the method to the study of chronic lymphocytic leukemia and T cell acute lymphoblastic leukemia.
NATURE BIOTECHNOLOGY
(2023)
Article
Engineering, Biomedical
Furkan Gokce, Alicia Kaestli, Christian Lohasz, Martina de Geus, Hans-Michael Kaltenbach, Kasper Renggli, Beat Bornhauser, Andreas Hierlemann, Mario Modena
Summary: Despite improving survival rates in pediatric leukemia patients, the outcome for certain subtypes remains poor. A microphysiological drug-testing platform has been developed to address the limitations of current screening methods, allowing for the co-culture of patient-derived leukemia cells, bone marrow cells, and liver tissues. By testing the activation of the prodrug ifosfamide in this platform, sample-specific sensitivities to ifosfamide in primary leukemia samples can be identified, providing potential for precision chemotherapy selection.
ADVANCED HEALTHCARE MATERIALS
(2023)
Article
Medical Laboratory Technology
Carmen Burki, Martin Volleberg, Linnea Blomgren, Sean Froese, Martin Hersberger
Summary: This study presents a method for removing macroenzymes through precipitation with polyethylene glycol and proposes criteria for identifying their presence. Cut-off values for precipitation activity were determined for eight routine enzyme activities, and two macroenzymes were identified using gel filtration chromatography.
PRACTICAL LABORATORY MEDICINE
(2023)
Editorial Material
Endocrinology & Metabolism
Shamima Rahman, Marc Patterson, Verena Peters, Eva Morava, Johannes Zschocke, Matthias Baumgartner
JOURNAL OF INHERITED METABOLIC DISEASE
(2023)
Article
Cell Biology
Ziad Hassan, David Coelho, Carine Bossenmeyer-Pourie, Karim Matmat, Carole Arnold, Aurelie Savladori, Jean-Marc Alberto, Remy Umoret, Jean-Louis Gueant, Gregory Pourie
Summary: Impairment of one-carbon metabolism during pregnancy, either due to nutritional deficiencies in B9 or B12 vitamins or caused by specific genetic defects, is often associated with neurological defects, including cognitive dysfunction that persists even after vitamin supplementation. Using a knock-out model for the methionine synthase specifically in the brain, researchers found that the absence of methionine synthase did not lead to growth retardation in offspring. However, there were temporary retardations in vegetative functions during the suckling period and a significant reduction in cognitive performance after weaning. Investigation also showed a reduction of AMPA receptors phosphorylation and clustering in cognitive areas, indicating an epigenomic effect of the neuronal deficiency of methionine synthase on the reduction of glutamatergic synapses excitability.
Article
Biochemistry & Molecular Biology
Marie Lucienne, Raffaele Gerlini, Birgit Rathkolb, Julia Calzada-Wack, Patrick Forny, Stephan Wueest, Andres Kaech, Florian Traversi, Merima Forny, Celine Burer, Antonio Aguilar-Pimentel, Martin Irmler, Johannes Beckers, Sven Sauer, Stefan Koelker, Joseph P. Dewulf, Guido T. Bommer, Daniel Hoces, Valerie Gailus-Durner, Helmut Fuchs, Jan Rozman, D. Sean Froese, Matthias R. Baumgartner, Martin Hrabe de Angelis
Summary: Inherited disorders of mitochondrial metabolism, such as isolated methylmalonic aciduria, disrupt energy-producing pathways and pose challenges to energetic homeostasis. The study on a mouse model of methylmalonyl-CoA mutase (Mmut)-type methylmalonic aciduria revealed reduced appetite, energy expenditure, body mass, and altered adipose tissue functioning. The findings provide insights into energy imbalance in methylmalonic aciduria and have implications for disease understanding and patient management.
HUMAN MOLECULAR GENETICS
(2023)
Editorial Material
Endocrinology & Metabolism
Verena Peters, Matthias Baumgartner, Sean Froese, Eva Morava, Marc Patterson, Johannes Zschocke, Shamima Rahman
JOURNAL OF INHERITED METABOLIC DISEASE
(2023)
Article
Oncology
Karim Matmat, Jean-Baptiste Conart, Paul-Henri Graindorge, Sandra El Kouche, Ziad Hassan, Youssef Siblini, Remy Umoret, Ramia Safar, Okan Baspinar, Aurelie Robert, Jean-Marc Alberto, Abderrahim Oussalah, David Coelho, Jean-Louis Gueant, Rosa-Maria Gueant-Rodriguez
Summary: This study used an original mouse model to investigate cblG inherited retinopathy and found that altered DNA methylation plays a pivotal role in eye development, cone differentiation, and retinoid metabolism.
CLINICAL EPIGENETICS
(2023)
Article
Biochemical Research Methods
Yun Huang, Aneta Drakul, Jasmeet Sidhu, Kerstin K. Rauwolf, James Kim, Beat Bornhauser, Jean-Pierre Bourquin
Summary: Mesenchymal stromal cells (MSCs) play a crucial role in regulating hematopoiesis and may also support cancer cells in evading therapy. This study engineered MSCs to express a synthetic CD19-sensor receptor, allowing for ex vivo drug response profiling of primary CD19+ leukemia cells.
Article
Hematology
Malwine J. Barz, Lena Behrmann, Danaelle Capron, Gabriele Zuchtriegel, Fabio D. Steffen, Leo Kunz, Yang Zhang, Iria Jimenez Vermeerbergen, Blerim Marovca, Moritz Kirschmann, Antonia Zech, Cesar Nombela-Arrieta, Urs Ziegler, Timm Schroeder, Beat Bornhauser, Jean -Pierre Bourquin
Summary: Persistence of residual disease after induction chemotherapy is a strong predictor of relapse in acute lymphoblastic leukemia (ALL). Bone marrow microenvironment plays a role in treatment resistance. By using three-dimensional fluorescence imaging, specific sites in the bone marrow were identified where B-cell precursor ALL cells and T-ALL cells preferentially reside and interact with different components of the microenvironment. These lineage-dependent differences suggest potential targets for improving treatment.
Meeting Abstract
Endocrinology & Metabolism
Patrick Forny, Ximena Bonilla, David Lamparter, Wenguang Shao, Tanja Plessl, Caroline Frei, Anna Bingisser, Sandra Goetze, Audrey Van Drogen, Keith Harshman, Patrick Pedrioli, Florian Traversi, Ioannis Xenarios, Ruedi Aebersold, Nicola Zamboni, Gunnar Ratsch, Emmanouil Dermitzakis, Bernd Wollscheid, D. Sean Froese, Matthias R. Baumgartner
MOLECULAR GENETICS AND METABOLISM
(2022)