Article
Biochemistry & Molecular Biology
Edward A. Dennis
Summary: Lipids play important roles in chronic diseases, but defining the substrate specificity of lipid metabolism enzymes is challenging. This research focuses on how membranes interact with enzymes to regulate cell signaling and metabolic pathways. By using substrate lipidomics and molecular dynamics simulations, the study reveals the link between enzyme specificity and hydrophobic binding subsites for membrane phospholipid substrates.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Multidisciplinary Sciences
Naoto Soya, Haijin Xu, Ariel Roldan, Zhengrong Yang, Haoxin Ye, Fan Jiang, Aiswarya Premchandar, Guido Veit, Susan P. C. Cole, John Kappes, Tamas Hegedus, Gergely L. Lukacs
Summary: The folding and rescuing of multidomain ABC transporters have significant implications for organismal health. In this study, the authors employed molecular dynamic simulations, biochemical and hydrogen deuterium exchange approaches to investigate the mechanisms underlying the folding and rescue of ABCC transporters. It was found that modulating the interfaces between the nucleotide binding domains and transmembrane domains could affect the posttranslational coupled domain-folding in the endoplasmic reticulum. Furthermore, the use of folding correctors could rescue the folding intermediates of CFTR mutants by rewiring inter-domain allosteric networks.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Peter G. Miller, Murugappan Sathappa, Jamie A. Moroco, Wei Jiang, Yue Qian, Sumaiya Iqbal, Qi Guo, Andrew O. Giacomelli, Subrata Shaw, Camille Vernier, Besnik Bajrami, Xiaoping Yang, Cerise Raffier, Adam S. Sperling, Christopher J. Gibson, Josephine Kahn, Cyrus Jin, Matthew Ranaghan, Alisha Caliman, Merissa Brousseau, Eric S. Fischer, Robert Lintner, Federica Piccioni, Arthur J. Campbell, David E. Root, Colin W. Garvie, Benjamin L. Ebert
Summary: This study elucidates the molecular mechanism of GSK2830371 activity by using computational, biochemical and functional genetic studies. The data shows that GSK2830371 binds to an allosteric site of PPM1D with high affinity and shifts the equilibrium to the inactive form. Additionally, it is found that C-terminal truncating mutations destabilize the protein. These findings provide insights into the biology of PPM1D.
NATURE COMMUNICATIONS
(2022)
Article
Chemistry, Medicinal
Juan P. Rincon Pabon, Brent A. Kochert, Yan-Hui Liu, Douglas D. Richardson, David D. Weis
Summary: Affinity chromatography is widely used for antibody purification in biopharmaceutical production, and here we used hydrogen exchange-mass spectrometry to study the conformational changes in the NIST mAb upon binding with a protein A matrix. The results showed increased protection in certain regions of the antibody structure when bound to ProA, but this effect was not observed with lower ProA concentration or when ProA resin was used.
JOURNAL OF PHARMACEUTICAL SCIENCES
(2021)
Article
Geosciences, Multidisciplinary
T. Shreve, Y. Zhan, H. Le Mevel, D. Roman, Y. Moussallam
Summary: This study identifies two distinct magma reservoirs beneath Ambrym volcano in Vanuatu. The pressure changes indicate that these reservoirs may not currently be hydraulically connected, which provides further insight into the changes of magmatic plumbing systems after rift-zone eruptions.
GEOPHYSICAL RESEARCH LETTERS
(2023)
Article
Biochemistry & Molecular Biology
Monika Kish, Sivaraman Subramanian, Victoria Smith, Natasha Lethbridge, Lindsay Cole, Frank Vollmer, Nicholas. J. Bond, Jonathan J. Phillips
Summary: The regulation of Glycogen phosphorylase (GlyP) is achieved through the "order-disorder" transition of its active site, providing insights into its structural regulation.
Article
Plant Sciences
Tahrim Ramzan, Muhammad Shahbaz, Muhammad Faisal Maqsood, Usman Zulfiqar, Rafia Urooj Saman, Nian Lili, Muhammad Irshad, Sana Maqsood, Arslan Haider, Babar Shahzad, Abdel-Rhman Z. Gaafar, Fasih Ullah Haider
Summary: This study aimed to evaluate the effects of phenylalanine (PA) on mustard plants under drought stress. The results showed that foliar application of PA helped to overcome the losses caused by drought and improved the shoot length, chlorophyll contents, and yield of mustard plants. It also reduced oxidative damage and electrolyte leakage. However, further research is needed to examine the impacts of PA on open-field-grown mustard crops.
PLANT PHYSIOLOGY AND BIOCHEMISTRY
(2023)
Article
Multidisciplinary Sciences
Guochao Wei, Naseer Iqbal, Valentine V. Courouble, Ashwanth C. Francis, Parmit K. Singh, Arpa Hudait, Arun S. Annamalai, Stephanie Bester, Szu-Wei Huang, Nikoloz Shkriabai, Lorenzo Briganti, Reed Haney, Vineet N. KewalRamani, Gregory A. Voth, Alan N. Engelman, Gregory B. Melikyan, Patrick R. Griffin, Francisco Asturias, Mamuka Kvaratskhelia
Summary: This study highlights the importance of prion-like low complexity domains in binding and increasing the avidity when interacting with viral capsid, through structural, biochemical, and virological assays.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Huwenbo Shi, Steven Gazal, Masahiro Kanai, Evan M. Koch, Armin P. Schoech, Katherine M. Siewert, Samuel S. Kim, Yang Luo, Tiffany Amariuta, Hailiang Huang, Yukinori Okada, Soumya Raychaudhuri, Shamil R. Sunyaev, Alkes L. Price
Summary: The study identifies that trans-ethnic genetic correlation is significantly less than 1 for many diseases, limiting trans-ethnic polygenic risk prediction. Causal effect sizes are found to be more population-specific in functionally important regions, with skin and immune genes showing the highest population-specificity.
NATURE COMMUNICATIONS
(2021)
Article
Geriatrics & Gerontology
Ranu Pal, Dongwei Hui, Heather Menchen, Huiping Zhao, Olivier Mozziconacci, Heather Wilkins, Brian S. J. Blagg, Christian Schoneich, Russell H. Swerdlow, Mary L. Michaelis, Elias K. Michaelis
Summary: A common feature of neurodegenerative diseases is the presence of mis-folded proteins that form aggregates, indicating suboptimal activity of neuronal molecular chaperones. The study found that KU-32, a novobiocin analog, provides strong protection against amyloid beta-induced neuronal death. KU-32 reverses the oxidative stress caused by amyloid beta and improves mitochondrial metabolism by inhibiting PDHK.
FRONTIERS IN AGING NEUROSCIENCE
(2023)
Review
Biochemistry & Molecular Biology
Matthew A. H. Parson, Meredith L. Jenkins, John E. Burke
Summary: This review discusses the application of Hydrogen-deuterium exchange mass spectrometry (HDX-MS) as a powerful biophysical tool for studying the structure and function of intrinsically disordered regions in proteins. The focus is on the theory of hydrogen exchange and its practical application in identifying disordered regions and characterizing their involvement in protein-protein and protein-membrane interfaces.
BIOCHEMICAL SOCIETY TRANSACTIONS
(2022)
Article
Multidisciplinary Sciences
Fanindra Kumar Deshmukh, Gili Ben-Nissan, Maya A. Olshina, Maria G. Fuzesi-Levi, Caley Polkinghorn, Galina Arkind, Yegor Leushkin, Irit Fainer, Sarel J. Fleishman, Dan Tawfik, Michal Sharon
Summary: Controlled degradation of proteins is crucial for maintaining a healthy proteome. A family of proteins called Catalytic Core Regulators (CCRs) has been discovered to regulate the function of the 20S proteasome through an allosteric mechanism. The physical binding of the PSMB4 subunit attenuates the proteolytic activities of the proteasome. This finding sheds light on a novel allosteric pathway that can be targeted for developing selective 20S proteasome inhibitors and uncoupling the degradation pathways of 20S and 26S proteasomes.
NATURE COMMUNICATIONS
(2023)
Article
Genetics & Heredity
YanYan Ma, YaoGang Zhang, Tao Zhang, Zhu Man, XiaoMing Su, ShuJing Hao, TianZe Wang
Summary: This study identified a practical enzymatic diagnostic method for PDHC-related mitochondrial diseases through peripheral blood leukocyte PDHC activity assay and gene mutation analysis. The results showed a dramatically decreased PDHC activity and the identification of a missense mutation in the PDHC gene, providing insights for clinical diagnosis of PDHC deficiency.
MOLECULAR GENETICS & GENOMIC MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Dennis S. Winston, Scott D. Gorman, David D. Boehr
Summary: Conformational fluctuations are important for protein function and allosteric regulation. In this study, NMR experiments were used to investigate the conformational dynamics of ScCM. The results suggest that the two-state MWC model is insufficient to explain the conformational dynamics of ScCM, and tyrosine and tryptophan have different effects on the conformational fluctuations.
JOURNAL OF MOLECULAR BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Simon A. Cobbold, Madel Tutor, Philip Frasse, Emma McHugh, Markus Karnthaler, Darren J. Creek, Audrey Odom John, Leann Tilley, Stuart A. Ralph, Malcolm J. McConville
Summary: This study used multiplex C-13-labelling coupled with untargeted mass spectrometry to generate a draft metabolome of P. falciparum and its host erythrocyte. It identified previously uncharacterized enzymes crucial for parasite development and proliferation, as well as highlighted the activity of metabolite repair pathways in rapidly growing parasite stages, suggesting new opportunities for drug discovery.
MOLECULAR SYSTEMS BIOLOGY
(2021)