Review
Cell Biology
Jara Lascorz, Joan Codina-Fabra, David Reverter, Jordi Torres-Rosell
Summary: Post-translational modification by SUMO proteins involves non-covalent interactions with other proteins, which play crucial roles in regulating protein activity, localization, and stability.
SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY
(2022)
Article
Cell Biology
Heather L. Martin, Amy L. Turner, Julie Higgins, Anna A. Tang, Christian Tiede, Thomas Taylor, Sitthinon Siripanthong, Thomas L. Adams, Iain W. Manfield, Sandra M. Bell, Ewan E. Morrison, Jacquelyn Bond, Chi H. Trinh, Carolyn D. Hurst, Margaret A. Knowles, Richard W. Bayliss, Darren C. Tomlinson
Summary: This study reveals a new mechanism of kinase inhibition by capturing the intermediate activation state of PAK5. It provides a potential therapeutic target for urothelial cancer cells and suggests that inhibiting PAK5 could have anti-tumor effects on cell survival and proliferation.
Review
Chemistry, Medicinal
Junxia Wei, Huijing Wang, Qinwen Zheng, Jifa Zhang, Zhichao Chen, Jiaxing Wang, Liang Ouyang, Yuxi Wang
Summary: This review summarizes the role of SENP1 in tumorigenesis and development, focusing on the design and discovery of small molecule inhibitors. It provides ideas for the future development and research of SENP1 inhibitors.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Biochemical Research Methods
Zongqing Huang, Haoju Hua, Xiuzhen Du, Zipeng Zhen, Wei Zhao, Jun Feng, Ji-an Li
Summary: This study successfully isolated VHHs against the SUMO protein for the first time using biopanning of an immune camelid nanobody library. The VHHs were coupled to agarose resins to form affinity chromatography resins, allowing for one-step purification of various SUMO fusions.
JOURNAL OF CHROMATOGRAPHY A
(2024)
Article
Biochemical Research Methods
Brendan M. Floyd, Kevin Drew, Edward M. Marcotte
Summary: Protein phosphorylation is a crucial regulatory mechanism in eukaryotic cellular processes, with the majority of phosphorylation sites still having unknown functions. A method called phospho-DIFFRAC was developed to systematically identify phosphorylation-dependent protein assemblies and found that these interactions are enriched in RNA-binding proteins.
JOURNAL OF PROTEOME RESEARCH
(2021)
Article
Medicine, Research & Experimental
Fanghua Ye, Wen Zhang, Chenying Fan, Jiajia Dong, Min Peng, Wenjun Deng, Hui Zhang, Liangchun Yang
Summary: GSDME-mediated pyroptosis may be a novel aspect of the antileukemic effect of Bcl-2 inhibitors. This finding offers new insights into potential biomarkers and therapeutic strategies, identifying an important mechanism explaining the clinical activity of venetoclax and HMAs in AML.
JOURNAL OF TRANSLATIONAL MEDICINE
(2023)
Article
Chemistry, Multidisciplinary
Louise Plais, Alice Lessing, Michelle Keller, Adriano Martinelli, Sebastian Oehler, Gabriele Bassi, Dario Neri, Joerg Scheuermann
Summary: DNA-encoded chemical libraries (DELs) are valuable for discovering small molecule ligands to pharmaceutical protein targets. Compared to single-pharmacophore DELs, dual-pharmacophore DELs display two chemical moieties on both DNA strands simultaneously, allowing for diverse and pure library construction, with potential for targeting larger protein surfaces.
Article
Biochemistry & Molecular Biology
Jose A. Villegas, Tasneem M. Vaid, Michael E. Johnson, Terry W. Moore
Summary: A major challenge in computational modeling of macromolecules is the vast conformational space due to atomic degrees of freedom. Recent interest in predictive models of complexes mediated by PROTACs led to the application of advanced computational techniques. However, repurposing existing tools for protein-protein docking and linker conformer generation results in incompatible structures. In this study, a cyclic coordinate descent algorithm was used to position PROTACs into complex-bound configurations, allowing for a restricted search in protein-protein conformations that can be bridged by a PROTAC molecule with a given linker composition.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2023)
Article
Chemistry, Medicinal
Merlin Bresinsky, Jessica M. Strasser, Alexander Hubmann, Bernadette Vallaster, William M. McCue, Jessica Fuller, Gurpreet Singh, Kathryn M. Nelson, Matthew E. Cuellar, Barry C. Finzel, Karen H. Ashe, Michael A. Walters, Steffen Pockes
Summary: This article describes the design and research of Casp2 inhibitors. By synthesizing peptide molecules and conducting in vitro experiments and molecular modeling, the researchers discovered some molecules with selective Casp2 and Casp3 inhibitory abilities. This study provides a reasonable basis for the development of selective Casp2 and Casp3 inhibitors.
ARCHIV DER PHARMAZIE
(2022)
Article
Biochemistry & Molecular Biology
Chang-Heng Hsieh, Chia-Cheng Chou, Ya-Ching Fang, Po-Hao Hsu, Yi-Hung Chiu, Chi-Sheng Yang, Guey-Mei Jow, Chih-Yung Tang, Chung-Jiuan Jeng
Summary: Endogenous 14-3-3 proteins play a chaperone-like role in regulating the stability of Eag1 protein and modulators of 14-3-3 have therapeutic potential in correcting protein expression of disease-causing Eag1 mutants.
CELL AND BIOSCIENCE
(2023)
Article
Chemistry, Multidisciplinary
Peter J. Cossar, Madita Wolter, Lars van Dijck, Dario Valenti, Laura M. Levy, Christian Ottmann, Luc Brunsveld
Summary: The study emphasizes the importance of considering the selectivity of stabilizer molecules in addition to their potency. Targeting the phosphorylated motifs on 14-3-3 hub proteins can lead to the stabilization of specific protein-protein interactions and drive selective PPI stabilization through cooperative complex formation.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Biochemistry & Molecular Biology
Ji Seon Lee, Jung Eun Min, Hun Jee Choe, Kyong Soo Park, Sung Soo Chung
Summary: The study investigates the regulation of lipid droplet size in adipocytes by SENP2. The results demonstrate that over-expression of SENP2 increases lipid droplet size and facilitates CIDEA transcription. SENP2 mainly enhances CIDEA expression by modulating ERRα, thereby increasing lipid droplet size in adipocytes.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2023)
Review
Biochemistry & Molecular Biology
Pavel V. Ershov, Yuri V. Mezentsev, Alexis S. Ivanov
Summary: The identification of disease-related protein-protein interactions (PPIs) allows for objective modulation of these interactions. Recent progress in interfacial peptide design has overcome specific challenges associated with targeted delivery and binding to cellular targets, leading to promising therapeutic formulations that are currently being investigated in clinical trials.
Article
Cell Biology
Christopher Ptak, Natasha O. Saik, Ashwini Premashankar, Diego L. Lapetina, John D. Aitchison, Ben Montpetit, Richard W. Wozniak
Summary: This study investigates the regulation mechanism of chromatin interaction with the inner nuclear membrane in yeast, revealing phosphorylation-dependent SUMOylation events that positively regulate chromatin binding. Specifically, a phosphorylation-mediated targeting mechanism of the SUMO ligase Siz2 to the inner nuclear membrane during mitosis is identified, involving the SUMOylation of the VAP protein Scs2 and supporting the assembly and anchorage of subtelomeric chromatin.
JOURNAL OF CELL BIOLOGY
(2021)
Article
Chemistry, Organic
Jin-Yi Liu, Shi-Yi Zhuang, Yong-Xing Tang, Xiang-Long Chen, You Zhou, Yan-Dong Wu, Kai-Lu Zheng, An-Xin Wu
Summary: An I-2-DMSO-mediated multicomponent [3+1+2] cascade annulation reaction using aryl methyl ketones, enaminones, and benzo[d]isoxazol-3-amine as substrates has been developed. This metal-free reaction involved the transannulation of benzo[d]isoxazol-3-amines with the formation of two C-N bonds and a C-C bond in one pot. The target product with a phenolic hydroxyl group could undergo further modification with pharmaceuticals, showing the utility of this method.
JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Nanoscience & Nanotechnology
Arindam Pramanik, Zexi Xu, Shazana H. Shamsuddin, Yazan S. Khaled, Nicola Ingram, Thomas Maisey, Darren Tomlinson, P. Louise Coletta, David Jayne, Thomas A. Hughes, Arwen I. I. Tyler, Paul A. Millner
Summary: Scientists have developed a targeted drug delivery system based on lyotropic liquid crystalline nanoparticles and demonstrated its high specificity and therapeutic efficacy for colorectal cancer through preclinical studies.
ACS APPLIED MATERIALS & INTERFACES
(2022)
Article
Chemistry, Analytical
Hope Adamson, Modupe O. Ajayi, Kate E. Gilroy, Michael J. McPherson, Darren C. Tomlinson, Lars J. C. Jeuken
Summary: C. difficile infection is a serious healthcare-associated disease and the development of a reliable point-of-care test is urgently needed. This study combines binding proteins and NanoBiT technology to develop a highly sensitive assay for the rapid diagnosis of true CDI.
ANALYTICAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Katherine L. Harper, Timothy J. Mottram, Chinedu A. Anene, Becky Foster, Molly R. Patterson, Euan McDonnell, Andrew Macdonald, David Westhead, Adrian Whitehouse
Summary: Non-coding RNA regulatory networks play a critical role in gene expression, modulating multiple cellular pathways and impacting various diseases. A novel host ncRNA regulatory network essential for KSHV lytic replication in B cells involves KSHV-mediated upregulation of host cell circHIPK3, acting as a competing endogenous RNA of miR-30c and leading to increased levels of DLL4. Dysregulation of this network during KSHV lytic replication highlights a novel mechanism of cell cycle control.
Article
Biochemical Research Methods
Konstantin Roder, Amy M. Barker, Adrian Whitehouse, Samuela Pasquali
Summary: This article investigates the change in structure of an RNA regulatory molecule upon a change in the chemistry of one of its bases. The results show that a chemical modification can induce a global rearrangement of the structure, affecting regions far away from the modification site.
PLOS COMPUTATIONAL BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Namrita Kaur, Andrea Ruiz-Velasco, Rida Raja, Gareth Howell, Jessica M. Miller, Riham R. E. Abouleisa, Qinghui Ou, Kimberly Mace, Susanne S. Hille, Norbert Frey, Pablo Binder, Craig P. Smith, Helene Fachim, Handrean Soran, Eileithyia Swanton, Tamer M. A. Mohamed, Oliver J. Mueller, Xin Wang, Jonathan Chernoff, Elizabeth J. Cartwright, Wei Liu
Summary: Myocardial inflammation contributes to cardiomyopathy in diabetic patients, primarily through inflammation induced by abnormal ER. Studies have revealed that ER stress-induced CHOP is a novel regulator of HMGB1 in the heart, with HMGB1 release promoting macrophage polarization and aggravating myocardial inflammation.
Review
Cell Biology
Paul Cordell, Glenn Carrington, Alistair Curd, Francine Parker, Darren Tomlinson, Michelle Peckham
Summary: Antibodies, nanobodies, and Affimers are tools used for labeling molecules in cells. Nanobodies and Affimers have advantages over traditional antibodies due to their small size, high binding affinity, and ability to penetrate dense cellular regions. They are expected to become the preferred tools for super-resolution imaging.
JOURNAL OF CELL SCIENCE
(2022)
Article
Microbiology
Francis R. Hopkins, Beatriz Alvarez-Rodriguez, George R. Heath, Kyriakoulla Panayi, Samantha Hover, Thomas A. Edwards, John N. Barr, Juan Fontana
Summary: Bunyaviruses are emerging RNA viruses that cause significant disease and economic burden and for which vaccines or therapies approved for humans are not available. The bunyavirus genome is wrapped up by the nucleoprotein (NP) and interacts with the viral polymerase, forming a ribonucleoprotein (RNP). This is the only form of the genome active for viral replication and assembly. However, until now how NPs are organized within an RNP was not known for any orthobunyavirus. Here, we purified RNPs from the prototypical orthobunyavirus, Bunyamwera virus, and employed microscopy approaches to show that the NP portion of the RNP was helical. We then combined our helical average with the known structure of an NP monomer, generating a pseudo-atomic model of this region. This arrangement allowed the RNPs to be highly flexible, which was critical for several stages of the viral replication cycle, such as segment circularization.
Article
Multidisciplinary Sciences
James C. Murphy, Elena M. Harrington, Sophie Schumann, Elton J. R. Vasconcelos, Timothy J. Mottram, Katherine L. Harper, Julie L. Aspden, Adrian Whitehouse
Summary: Historically, ribosomes were thought to be homogeneous machines lacking regulatory capacity, but recent discoveries have uncovered the existence of compositionally distinct, specialized ribosomes that actively regulate mRNA translation. This study focuses on the manipulation of ribosome biogenesis by KSHV to generate specialized ribosomes for efficient translation of viral mRNAs.
NATURE COMMUNICATIONS
(2023)
Article
Cardiac & Cardiovascular Systems
Francine Parker, Anna A. S. Tang, Brendan Rogers, Glenn Carrington, Cris dos Remedios, Amy Li, Darren Tomlinson, Michelle Peckham
Summary: Dilated Cardiomyopathy (DCM) is a common type of heart failure that affects the structure and organization of heart muscles. This study used Affimers to examine the proteins associated with Z-discs and transitional junctions in DCM patients. The use of Affimers improved the resolution of microscopy images and revealed new structural details in failing hearts. Affimers are a valuable tool for studying changes in cardiomyocyte structure and organization in diseased hearts.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Barnaby W. R. Roper, Christian Tiede, Izma Abdul-Zani, Gary A. Cuthbert, Dhananjay Jade, Ahmed Al-Aufi, William R. Critchley, Queen Saikia, Shervanthi Homer-Vanniasinkam, Tatsuya Sawamura, Michael J. Mcpherson, Michael A. Harrison, Darren C. Tomlinson, Sreenivasan Ponnambalam
Summary: In multicellular organisms, lipid-protein particles regulate the flow of lipids and fatty acids between cells. Oxidation of these particles triggers pathological responses mediated by scavenger receptors. This study identified synthetic proteins, termed Affimers, that specifically bind to oxidized low-density lipoprotein (oxLDL) and inhibit its binding and uptake by cells expressing LOX-1. The findings provide insights into vascular diseases and can contribute to further understanding of related pathologies.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2023)
Article
Cell Biology
Heather L. Martin, Amy L. Turner, Julie Higgins, Anna A. Tang, Christian Tiede, Thomas Taylor, Sitthinon Siripanthong, Thomas L. Adams, Iain W. Manfield, Sandra M. Bell, Ewan E. Morrison, Jacquelyn Bond, Chi H. Trinh, Carolyn D. Hurst, Margaret A. Knowles, Richard W. Bayliss, Darren C. Tomlinson
Summary: This study reveals a new mechanism of kinase inhibition by capturing the intermediate activation state of PAK5. It provides a potential therapeutic target for urothelial cancer cells and suggests that inhibiting PAK5 could have anti-tumor effects on cell survival and proliferation.
Article
Biotechnology & Applied Microbiology
Richard E. Randall, Dan F. Young, David J. Hughes, Steve Goodbourn
Summary: Parainfluenza virus type 5 (PIV5) can have either a persistent or a lytic phenotype in cultured cells, depending on the phosphorylation status of the phosphoprotein (P). In co-infections, the persistent phenotype is dominant and the virus particles can package multiple genomes. Both lytic and persistent genotypes can be maintained in co-infected cells and individual colonies derived from persistently infected cells.
JOURNAL OF GENERAL VIROLOGY
(2023)
Article
Biochemistry & Molecular Biology
Fruzsina Hobor, Zsofia Hegedus, Amaurys Avila Ibarra, Vencel L. Petrovicz, Gail J. Bartlett, Richard B. Sessions, Andrew J. Wilson, Thomas A. Edwards
Summary: The hypoxic response is crucial for cell function and vital in the growth and survival of solid tumors. HIF-1 regulates this response by activating over 100 genes responsible for adapting to hypoxia, making it a potential target for anticancer drug discovery. This study investigates the sequence determinants of the binding between HIF-1 alpha and p300, as well as negative regulators of HIF-1 alpha such as CITED2. The findings suggest that the HIF-1 alpha sequence is highly tolerant to sequence variation, and the binding interaction is controlled by backbone interactions and ligand folding.
RSC CHEMICAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Kristina Hetherington, Som Dutt, Amaurys A. Ibarra, Emma E. Cawood, Fruzsina Hobor, Derek N. Woolfson, Thomas A. Edwards, Adam Nelson, Richard B. Sessions, Andrew J. Wilson
Summary: The study introduces a computationally validated workflow for modifying the sequence of peptide inhibitors of protein-protein interactions.
RSC CHEMICAL BIOLOGY
(2021)