Article
Multidisciplinary Sciences
Yanli Dong, Hang Li, Alina Ilie, Yiwei Gao, Annie Boucher, Xuejun Cai Zhang, John Orlowski, Yan Zhao
Summary: Sodium-proton exchanger 3 (NHE3/SLC9A3) plays an important role in regulating salt and fluid absorption as well as pH homeostasis. Calcineurin B homologous protein 1 (CHP1) acts as an auxiliary regulatory factor for NHE3, promoting its maturation and plasmalemmal expression. Cryo-electron microscopy structure analysis revealed that a cytosolic helix-loop-helix motif in NHE3 inhibits substrate transport, and the binding of phosphatidylinositol molecules stabilizes the complex and enhances its transport activity.
Article
Chemistry, Organic
Dakoju Ravi Kishore, Chander Shekhar, Gedu Satyanarayana
Summary: This efficient and facile method utilizes Lewis acid catalysis to achieve the regioselective synthesis of novel dihydrobenzo[a]fluorenes from alkynols. Both secondary and tertiary alcohols bearing an alkyne moiety can be smoothly transformed into the corresponding products. Consequently, tetracyclic dihydrobenzo[a]fluorenes have been successfully synthesized using this approach.
JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Pharmacology & Pharmacy
Shotaro Michinaga, Ayaka Nagata, Ryosuke Ogami, Yasuhiro Ogawa, Shigeru Hishinuma
Summary: This study aimed to explore how H1 receptor-mediated ERK phosphorylation is regulated by Gq proteins and arrestins. The results showed that the Gq protein pathway mainly regulates early phosphorylation reaction, while the arrestin pathway mainly regulates late phosphorylation reaction.
BIOCHEMICAL PHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Alessio Ausili, Senena Corbalan-Garcia, Juan C. Gomez-Fernandez
Summary: The C2 domain of novel protein kinases C (nPKC) binds to membranes in a Ca2+-independent manner. Through various experiments, the strong interaction between the C2 domain and POPA was confirmed, as well as differences observed during thermal unfolding in the presence of phosphatidic acid or cardiolipin. Furthermore, the effect of membrane curvature on the domain/membrane interaction was investigated, showing that phospholipids do not exert their influence on protein binding through changes in membrane curvature.
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
(2021)
Article
Hematology
Rina Nishii, Rebekah Baskin-Doerfler, Wentao Yang, Ninad Oak, Xujie Zhao, Wenjian Yang, Keito Hoshitsuki, Mackenzie Bloom, Katherine Verbist, Melissa Burns, Zhenhua Li, Ting-Nien Lin, Maoxiang Qian, Takaya Moriyama, Julie M. Gastier-Foster, Karen R. Rabin, Elizabeth Raetz, Charles Mullighan, Ching-Hon Pui, Allen Eng-Juh Yeoh, Jinghui Zhang, Monika L. Metzger, Jeffery M. Klco, Stephen P. Hunger, Scott Newman, Gang Wu, Mignon L. Loh, Kim E. Nichols, Jun J. Yang
Summary: Research shows that germline ETV6 variants can affect susceptibility to acute lymphoblastic leukemia and lead to a novel leukemia predisposition syndrome. Variants in ETV6 impact DNA binding, transcriptional repressor activity, and nuclear localization, influencing the genomic landscape, karyotype, and gene expression patterns of leukemia cells.
Article
Cell Biology
Guowei Wu, Dekang Li, Wei Liang, Weimin Sun, Xingxing Xie, Yilun Tong, Bing Shan, Mengmeng Zhang, Xiaojuan Lu, Junying Yuan, Ying Li
Summary: Activation of TNFR1 by TNF alpha leads to the formation of complex I, which plays a crucial role in determining cell fate. This study identifies PP6 as a component of complex I and shows that it regulates cell death through its phosphatase activity and regulatory subunits. Mechanistic studies reveal that PP6 modulates LUBAC-mediated ubiquitination to promote RIPK1 activation and c-FLIPL degradation. Loss of PP6 due to melanoma-related mutations confers resistance to cell death and promotes cancer progression.
CELL DEATH & DISEASE
(2022)
Article
Pharmacology & Pharmacy
Yuwei Jiang, Jiaoya Xu, Ping Huang, Lili Yang, Yang Liu, Yiping Li, Jue Wang, Haiyan Song, Peiyong Zheng
Summary: This study confirms that mitochondrial dysfunction induced by the JNK/Sab signaling pathway plays a crucial role in the development of NASH. Scoparone, by suppressing this signaling pathway, can partially improve the lipotoxic liver injury, making it a potential therapeutic compound for NASH.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Chemistry, Organic
Rukhsar Gul, Liqun Hu, Yibing Liu, Youwei Xie
Summary: Here, we present highly efficient intramolecular hydroarylations mediated by Re2O7/HReO4. By using styrene derivatives with different electronic properties, a challenging intramolecular hydroarylation for the facile access to various substituted 1-aryltetralin structures was achieved. This method exhibits mild reaction conditions, broad substrate scope, high chemical yields, and 100% atom economy. The potential synthetic application of this methodology was demonstrated through the efficient total synthesis of an isoCA-4 analogue.
JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Chemistry, Organic
Lina Cai, Qihong Lai, Lele Zhang, Guotao Xue, Yirui Zhang, Na He, Mingqiang Huang, Shirong Hu, Shunyou Cai
Summary: This study presents an efficient and practical lanthanum-catalyzed reaction method for continuous epoxy-ring opening and oxidative dehydrogenative lactonization under visible-light irradiation. The lanthanum catalyst acts as both a Lewis acid and a photocatalyst in this reaction, eliminating the need for additional photocatalysts. The method allows for convenient preparation of isochromanones with oxygen-containing spirocyclic structural units.
Article
Biochemistry & Molecular Biology
Harvinder Singh, Anupam Raja, Nishant Shekhar, Arushi Chauhan, Ajay Prakash, Pramod Avti, Bikash Medhi
Summary: This study utilized computational modelling approaches to virtually screen small molecule libraries against the Ca2+-binding site of the PKC-γ-C2 regulatory domain. Two potential drug molecules, LIG-41 and LIG-16, were discovered with the potential to inhibit PKC-γ activity.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Neurosciences
Suzanne M. Underhill, Susan G. Amara
Summary: Stimulation of M-1/M-5 muscarinic receptors in midbrain cultures has been found to decrease the ability of dopamine neurons to transport dopamine through DAT. Cholinomimetic drugs lead to a decrease in DAT activity, while M-1/M-5-specific antagonists can block these effects, implicating M-1/M-5 receptors in the modulation of DAT function on dopamine neurons.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2021)
Editorial Material
Hematology
Jan A. Burger
Summary: The study reveals that MARCKS protein is differentially expressed in patients with chronic lymphocytic leukemia based on the mutation status of IGHV, and its expression and phosphorylation are linked to CLL cell migration through key signaling pathways. The findings were also confirmed in samples from patients treated with the BTK inhibitor acalabrutinib.
Article
Cell Biology
Desiree M. Baron, Adam R. Fenton, Sara Saez-Atienzar, Anthony Giampetruzzi, Aparna Sreeram, Shankaracharya, Pamela J. Keagle, Victoria R. Doocy, Nathan J. Smith, Eric W. Danielson, Megan Andresano, Mary C. McCormack, Jaqueline Garcia, Valerie Bercier, Ludo Van den Bosch, Jonathan R. Brent, Claudia Fallini, Bryan J. Traynor, Erika L. F. Holzbaur, John E. Landers
Summary: Understanding the pathogenic mechanisms of disease mutations is crucial for advancing treatments. This study found that ALS-associated mutations in the gene encoding microtubule motor KIF5A result in the production of a protein with an abnormal C-terminal sequence, leading to motor activity dysregulation and decreased neuronal survival. These findings shed light on the disruptive effects of pathogenic mutations on intracellular trafficking and neuronal homeostasis.
Article
Biochemistry & Molecular Biology
Liding Zhao, Ya Li, Tian Xu, Qingbo Lv, Xukun Bi, Xianglan Liu, Guosheng Fu, Yunzeng Zou, Junbo Ge, Zhaoyang Chen, Wenbin Zhang
Summary: This study found that diabetes mellitus plays a significant role in aggravating chronic inflammation and promoting atherosclerosis, in conjunction with hyperlipidemia. The mechanism of action may involve the induction of immune maturation of dendritic cells, likely through the RAGE-TLR4-PKC β(1) signaling pathway.
MOLECULAR MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Tania M. Palhano Zanela, Alexzandrea Woudenberg, Karen G. Romero Bello, Eric S. Underbakke
Summary: Pyk2 is a non-receptor tyrosine kinase that undergoes multistage activation mechanism, involving conformational rearrangements, autophosphorylation, and Src recruitment. By employing hydrogen/deuterium exchange mass spectrometry and kinase activity profiling, the conformational dynamics associated with substrate binding and Src-mediated activation loop phosphorylation were mapped. The phosphorylation-induced rearrangements elevate kinase activity above the basal autophosphorylation rate.
Review
Biochemistry & Molecular Biology
Gerga Gogl, Alexandr P. Kornev, Attila Remenyi, Susan S. Taylor
TRENDS IN BIOCHEMICAL SCIENCES
(2019)
Review
Biochemistry & Molecular Biology
Susan S. Taylor, Hiruy S. Meharena, Alexandr P. Kornev
Review
Biochemistry & Molecular Biology
Lalima G. Ahuja, Susan S. Taylor, Alexandr P. Kornev
Article
Multidisciplinary Sciences
Sven H. Schmidt, Matthias J. Knape, Daniela Boassa, Natascha Mumdey, Alexandr P. Kornev, Mark H. Ellisman, Susan S. Taylor, Friedrich W. Herberg
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2019)
Article
Multidisciplinary Sciences
Lalima G. Ahuja, Phillip C. Aoto, Alexandr P. Kornev, Gianluigi Veglia, Susan S. Taylor
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2019)
Article
Genetics & Heredity
Pedro M. Rodriguez Cruz, Judith Cossins, Jonathan Cheung, Susan Maxwell, Sandeep Jayawant, Ruth Herbst, Dominic Waithe, Alexandr P. Kornev, Jacqueline Palace, David Beeson
Review
Biochemistry & Molecular Biology
Susan S. Taylor, Jian Wu, Jessica G. H. Bruystens, Jason C. Del Rio, Tsan-Wen Lu, Alexandr P. Kornev, Lynn F. Ten Eyck
Summary: The Protein Data Bank has played a crucial role in the signaling community for over 30 years, facilitating information sharing between academics and industry. Through the study of protein kinases, particularly cAMP-dependent protein kinase, researchers have made significant discoveries including the importance of crystal packing in biological processes and disease relevance. Integrating crystallography with other techniques is opening up new possibilities for understanding intrinsically disordered regions and dynamic biological processes.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Timothy R. Baffi, Gema Lorden, Jacob M. Wozniak, Andreas Feichtner, Wayland Yeung, Alexandr P. Kornev, Charles C. King, Jason C. Del Rio, Ameya J. Limaye, Julius Bogomolovas, Christine M. Gould, Ju Chen, Eileen J. Kennedy, Natarajan Kannan, David J. Gonzalez, Eduard Stefan, Susan S. Taylor, Alexandra C. Newton
Summary: The study identified a mTOR-mediated phosphorylation site known as TOR interaction motif (TIM) that regulates the phosphorylation and activity of PKC and Akt. The TIM is invariant in mTORC2-dependent AGC kinases and plays a crucial role in kinase activity.
Article
Multidisciplinary Sciences
Alexandr P. Kornev, Phillip C. Aoto, Susan S. Taylor
Summary: The topological analysis of protein residue networks is a useful method for understanding the roles of individual residues. In this study, the researchers used protein kinase A as a study object and found that using local spatial pattern alignment could detect functionally important residues in the protein residue network.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Review
Chemistry, Physical
Lalima K. K. Madan, Colin L. L. Welsh, Alexandr P. P. Kornev, Susan S. S. Taylor
Summary: Allosteric regulation of proteins is an engaging research topic that has evolved from focusing on structural changes to considering internal protein dynamics. The violin model, based on redistribution of protein thermal fluctuations, utilizes graph theory and community network analysis to cluster correlated protein motions. This Review provides the theory and workflow of the methodology and illustrates its application to protein kinase A.
JOURNAL OF CHEMICAL PHYSICS
(2023)
Article
Biochemistry & Molecular Biology
Caila A. Pilo, Timothy R. Baffi, Alexandr P. Kornev, Maya T. Kunkel, Mario Malfavon, Dong-Hui Chen, Leigh -Ana Rossitto, Daniel X. Chen, Liang-Chin Huang, Cheryl Longman, Natarajan Kannan, Wendy H. Raskind, David J. Gonzalez, Susan S. Taylor, George Gorrie, Alexandra C. Newton
Summary: Spinocerebellar ataxia type 14 is a neurodegenerative disease caused by mutations in the PKCy gene, which disrupts the autoinhibition of the protein kinase and leads to cerebellar dysfunction.
Article
Biochemistry & Molecular Biology
Alexander C. Jones, Susan S. Taylor, Alexandra C. Newton, Alexandr P. Kornev
Meeting Abstract
Biophysics
Caila A. Pilo, Maya T. Kunkel, An-Angela N. Van, Evan K. Kobori, Alexandr P. Kornev, Cheryl Longman, George Gorrie, Susan S. Taylor, Alexandra C. Newton
BIOPHYSICAL JOURNAL
(2020)
Meeting Abstract
Biophysics
Alexandr P. Kornev
BIOPHYSICAL JOURNAL
(2020)
Meeting Abstract
Biochemistry & Molecular Biology
Lalima G. Ahuja, Yilin Meng, Alexandr P. Kornev, Benoit Roux, Susan Taylor