Article
Biochemistry & Molecular Biology
Antonio Galarreta, Pablo Valledor, Patricia Ubieto-Capella, Vanesa Lafarga, Eduardo Zarzuela, Javier Munoz, Marcos Malumbres, Emilio Lecona, Oscar Fernandez-Capetillo
Summary: Inhibitors of USP7 lead to widespread activation of CDK1 throughout the cell cycle, causing DNA damage and toxicity to mammalian cells. Additionally, USP7 interacts with the phosphatase PP2A, facilitating its active localization in the cytoplasm, and inhibition of USP7 or PP2A results in similar changes in the phosphoproteome, including increased phosphorylation of CDK1 targets.
Review
Biochemistry & Molecular Biology
Ni Made Pitri Susanti, Daryono Hadi Tjahjono
Summary: The cell cycle is crucial in cell development, and its progression is controlled by endogenous CDK inhibitors, CDKs, and cyclins. Dysregulation of the cell cycle can lead to cancer, making CDK a natural target for anticancer therapy. Understanding CDK structures and complexes with drugs helps in developing CDK inhibitors, from non-selective to selective CDK4/CDK6 inhibitors applied in clinical cancer treatment.
Article
Multidisciplinary Sciences
Arangasamy Yazhini, Narayanaswamy Srinivasan, Sankaran Sandhya
Summary: In this study, the whole proteome sequences of six Afrotherian species were compared, revealing high homologous proteins and predominant involvement in metabolism. Through rigorous sequence searches, 156 uncharacterized protein sequences and 28 species-specific proteins were annotated. The study also identified 141 unique functional domain architectures within Afrotheria, highlighting proteins with potential for specialized functions.
SCIENTIFIC REPORTS
(2021)
Article
Endocrinology & Metabolism
Ayush Midha, Hui Pan, Cristian Abarca, Joshua Andle, Priscila Carapeto, Susan Bonner-Weir, Cristina Aguayo-Mazzucato
Summary: Aging pancreatic beta-cells may develop a senescence-associated secretory phenotype (SASP) that can lead to dysfunction of neighboring cells through paracrine actions. The specific secretory profile of senescent beta-cells could have implications in both health and disease.
Article
Multidisciplinary Sciences
Cristian Thom, Janosch Ehrenmann, Santiago Vacca, Yann Waltenspuehl, Jendrik Schoeppe, Ohad Medalia, Andreas Plueckthun
Summary: The study reveals the structures of the neurokinin 1 receptor bound to its downstream signal mediators G(q) and G(s), as well as the conformational changes of the receptor under different ligand and antagonist actions.
Article
Biochemistry & Molecular Biology
Yasaman Rezvani, Caroline D. Keroack, Brendan Elsworth, Argenis Arriojas, Marc-Jan Gubbels, Manoj T. Duraisingh, Kourosh Zarringhalam
Summary: Babesia is a genus of parasites that infect red blood cells in vertebrate hosts. This study used single-cell RNA sequencing to analyze gene expression profiles of three Babesia species. The researchers identified co-expressed gene clusters and coordinated gene expression timing. They also reconstructed co-expression networks and found specific genes involved in the replication cycle. These findings contribute to our understanding of Babesia replication cycle progression and regulation.
Article
Multidisciplinary Sciences
Feng Wang, Bryant Chau, Sean M. West, Christopher R. Kimberlin, Fei Cao, Flavio Schwarz, Barbara Aguilar, Minhua Han, Winse Morishige, Christine Bee, Gavin Dollinger, Arvind Rajpal, Pavel Strop
Summary: Glucocorticoid-induced tumor necrosis factor receptor-related protein (GITR) and GITR ligand (GITRL) are members of the tumor necrosis superfamily that regulate immune cell activities, including anti-tumor immune responses. The structures and visualization of human and mouse GITR-GITRL complexes provide insights into the architecture of higher-order membrane assemblies and their signaling mechanisms.
NATURE COMMUNICATIONS
(2021)
Article
Chemistry, Multidisciplinary
Regina Freier, Eric Aragon, Radoslaw Pluta, Pau Martin-Malpartida, Lidia Ruiz, Miriam Condeminas, Cayetano Gonzalez, Maria J. Macias
Summary: Thioredoxins (Trxs) are ubiquitous enzymes that regulate the redox state in cells. In Drosophila, there are two germline-specific Trxs, Deadhead (Dhd) and thioredoxin T (TrxT), that have unique structural features which may guide future research on embryo development and redox homeostasis in fruit flies. These structures could also potentially be utilized for designing small-molecular binders to modulate native redox homeostasis and control plagues in Schizophora species.
Review
Cell Biology
Rustem Uzbekov, Claude Prigent
Summary: All living organisms are composed of cells, which undergo cell division to reproduce and form a whole organism. Cell division is a highly regulated process that follows a sequence of events known as the cell cycle. The universality of the cell cycle is attributed to the shared genetic information encoded by the DNA double helix in all organisms.
Article
Multidisciplinary Sciences
Carter J. Barger, Abigail K. Suwala, Katarzyna M. Soczek, Albert S. Wang, Min Y. Kim, Chibo Hong, Jennifer A. Doudna, Susan M. Chang, Joanna J. Phillips, David A. Solomon, Joseph F. Costello
Summary: TERT promoter duplications have the same functional significance as hotspot mutations, leading to tumor cell immortality, and are clonal in patients with multifocal glioblastoma.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Joshua M. Hardy, Natalee D. Newton, Naphak Modhiran, Connor A. P. Scott, Hariprasad Venugopal, Laura J. Vet, Paul R. Young, Roy A. Hall, Jody Hobson-Peters, Fasseli Coulibaly, Daniel Watterson
Summary: Using a chimeric platform, researchers have successfully and safely analyzed the structures of pathogenic flaviviruses, uncovering the presence of two lipid-like ligands within highly conserved pockets of the envelope protein's stem region that play a crucial role in virus maturation.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Yi Zhang, Yong-ping Xu, Ju-kui Nie, Hong Chen, Genji Qin, Bo Wang, Xiao-Dong Su
Summary: The crystal structures of TCP domains in complex with different dsDNA reveal their unique DNA-binding motif and three-site recognition mode. The TCP domains show broad specificity for DNA sequences even shorter than the consensus binding sites, adding complexity to the regulatory network of plant TCP transcription factors.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Biology
Seiji N. Sugiman-Marangos, Shivneet K. Gill, Michael J. Mansfield, Kathleen E. Orrell, Andrew C. Doxey, Roman A. Melnyk
Summary: Diphtheria toxin (DT) is a bacterial exotoxin that plays a central role in toxinology. However, the origins and evolutionary adaptation of DT to human hosts are still unknown. In this study, the researchers determined the high-resolution structures of DT homologs from Streptomyces albireticuli and Seinonella peptonophila. Despite not being toxic to human cells, these DT homologs displayed significant structural similarities to DT. The researchers found that the functional determinants of host range extended beyond cellular receptor binding, and differences in pH-induced pore formation and cytosolic release played a major role in toxin delivery into cells. This work provides insights into the expanding family of DT toxins and the mechanisms of host adaptation.
COMMUNICATIONS BIOLOGY
(2022)
Review
Oncology
Liguo Wang, Zhouli Yang, Guangchen Li, Yongbo Liu, Chao Ai, Yu Rao
Summary: This article summarizes the latest developments in CDK and cyclin protein degraders, covering their selectivity, application, validation, and the current state of development for CDK members lacking degraders. It provides a comprehensive overview for researchers in this field.
FRONTIERS OF MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Prasenjit Mondal, Saswat Mohapatra, Debmalya Bhunia, Prabir Kumar Gharai, Nabanita Mukherjee, Varsha Gupta, Satyajit Ghosh, Surajit Ghosh
Summary: Cell proliferation is a crucial step that may lead to cancer if not properly regulated, with p16 protein often remaining inactive in cancer cells. Researchers have focused on restoring the activity of p16 protein using new viral vectors, small molecules, and peptides to control abnormal cell proliferation. By conjugating a nuclear-localized signal (NLS) sequence and a short peptide (AVPI), the efficiency of p16 peptide as an anti-leukemia therapeutic agent has been significantly enhanced.
RSC MEDICINAL CHEMISTRY
(2022)
Article
Oncology
Steven R. Whittaker, Clare Barlow, Mathew P. Martin, Caterina Mancusi, Steve Wagner, Annette Self, Elaine Barrie, Robert Te Poele, Swee Sharp, Nathan Brown, Stuart Wilson, Wayne Jackson, Peter M. Fischer, Paul A. Clarke, Michael I. Walton, Edward McDonald, Julian Blagg, Martin Noble, Michelle D. Garrett, Paul Workman
MOLECULAR ONCOLOGY
(2018)
Article
Chemistry, Organic
Duncan C. Miller, Mathew P. Martin, Santosh Adhikari, Alfie Brennan, Jane A. Endicott, Bernard T. Golding, Ian R. Hardcastle, Amy Heptinstall, Stephen Hobson, Claire Jennings, Lauren Molyneux, Yvonne Ng, Stephen R. Wedge, Martin E. M. Noble, Celine Cano
ORGANIC & BIOMOLECULAR CHEMISTRY
(2018)
Article
Biochemical Research Methods
Liz Potterton, Jon Agirre, Charles Ballard, Kevin Cowtan, Eleanor Dodson, Phil R. Evans, Huw T. Jenkins, Ronan Keegan, Eugene Krissinel, Kyle Stevenson, Andrey Lebedev, Stuart J. McNicholas, Robert A. Nicholls, Martin Noble, Navraj S. Pannu, Christian Roth, George Sheldrick, Pavol Skubak, Johan Turkenburg, Ville Uski, Frank von Delft, David Waterman, Keith Wilson, Martyn Winn, Marcin Wojdyr
ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY
(2018)
Article
Chemistry, Multidisciplinary
Sanne J. M. Verhoork, Claire E. Jennings, Neshat Rozatian, Judith Reeks, Jieman Meng, Emily K. Corlett, Fazila Bunglawala, Martin E. M. Noble, Andrew G. Leach, Christopher R. Coxon
CHEMISTRY-A EUROPEAN JOURNAL
(2019)
Review
Biochemistry & Molecular Biology
Daniel J. Wood, Jane A. Endicott
Article
Chemistry, Medicinal
Daniel J. Wood, J. Daniel Lopez-Fernandez, Leanne E. Knight, Islam Al-Khawaldeh, Conghao Gai, Shengying Lin, Mathew P. Martin, Duncan C. Miller, Celine Cano, Jane A. Endicott, Ian R. Hardcastle, Martin E. M. Noble, Michael J. Waring
JOURNAL OF MEDICINAL CHEMISTRY
(2019)
Article
Chemistry, Medicinal
Stephanie M. Myers, Duncan C. Miller, Lauren Molyneux, Mercedes Arasta, Ruth H. Bawn, Timothy J. Blackburn, Simon J. Cook, Noel Edwards, Jane A. Endicott, Bernard T. Golding, Roger J. Griffin, Tim Hammonds, Ian R. Hardcastle, Suzannah J. Harnor, Amy B. Heptinstall, Pamela A. Lochhead, Mathew P. Martin, Nick C. Martin, David R. Newell, Paul J. Owen, Leon C. Pang, Tristan Reuillo, Laurent J. M. Rigoreau, Huw D. Thomas, Julie A. Tucker, Lan-Zhen Wang, Ai-Ching Wong, Martin E. M. Noble, Stephen R. Wedge, Celine Cano
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2019)
Letter
Biochemical Research Methods
Paul D. Adams, Pavel V. Afonine, Kumaran Baskaran, Helen M. Berman, John Berrisford, Gerard Bricogne, David G. Brown, Stephen K. Burley, Minyu Chen, Zukang Feng, Claus Flensburg, Aleksandras Gutmanas, Jeffrey C. Hoch, Yasuyo Ikegawa, Yumiko Kengaku, Eugene Krissinel, Genji Kurisu, Yuhe Liang, Dorothee Liebschner, Lora Mak, John L. Markley, Nigel W. Moriarty, Garib N. Murshudov, Martin Noble, Ezra Peisach, Irina Persikova, Billy K. Poon, Oleg V. Sobolev, Eldon L. Ulrich, Sameer Velankar, Clemens Vonrhein, John Westbrook, Marcin Wojdyr, Masashi Yokochi, Jasmine Y. Young
ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY
(2019)
Article
Multidisciplinary Sciences
Pamela A. Lochhead, Julie A. Tucker, Natalie J. Tatum, Jinhua Wang, David Oxley, Andrew M. Kidger, Victoria P. Johnson, Megan A. Cassidy, Nathanael S. Gray, Martin E. M. Noble, Simon J. Cook
NATURE COMMUNICATIONS
(2020)
Article
Biochemical Research Methods
Mathew P. Martin, Martin E. M. Noble
Summary: This article evaluates methods for validating and prioritizing crystallographic fragment screening results. Through retrospective analysis of an ATAD2 screening campaign and other successful fragment screening projects, a "triangulation" approach is suggested to develop qualitative structure-activity relationships (SARs) as an alternative to on-scale biophysical, biochemical, and/or biological measurements.
ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Daniel J. Wood, Svitlana Korolchuk, Natalie J. Tatum, Lan-Zhen Wang, Jane A. Endicott, Martin E. M. Noble, Mathew P. Martin
CELL CHEMICAL BIOLOGY
(2019)