Browsing Structural Biology by title
Now showing items 28-47 of 115
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Discovery of a Chemical Probe Bisamide (CCT251236): An Orally Bioavailable Efficacious Pirin Ligand from a Heat Shock Transcription Factor 1 (HSF1) Phenotypic Screen.
(AMER CHEMICAL SOC, 2017-01-12)Phenotypic screens, which focus on measuring and quantifying discrete cellular changes rather than affinity for individual recombinant proteins, have recently attracted renewed interest as an efficient strategy for drug ... -
Discovery of Potent, Selective, and Orally Bioavailable Small-Molecule Modulators of the Mediator Complex-Associated Kinases CDK8 and CDK19.
(AMER CHEMICAL SOC, 2016-02-11)The Mediator complex-associated cyclin-dependent kinase CDK8 has been implicated in human disease, particularly in colorectal cancer where it has been reported as a putative oncogene. Here we report the discovery of 109 ... -
Dissecting mechanisms of resistance to targeted drug combination therapy in human colorectal cancer.
(NATURE PUBLISHING GROUP, 2019-06-20)Genomic alterations in cancer cells result in vulnerabilities that clinicians can exploit using molecularly targeted drugs, guided by knowledge of the tumour genotype. However, the selective activity of these drugs exerts ... -
DNA origami-based single-molecule force spectroscopy elucidates RNA Polymerase III pre-initiation complex stability.
(NATURE PUBLISHING GROUP, 2020-06-05)The TATA-binding protein (TBP) and a transcription factor (TF) IIB-like factor are important constituents of all eukaryotic initiation complexes. The reason for the emergence and strict requirement of the additional ... -
E2/E3-independent ubiquitin-like protein conjugation by Urm1 is directly coupled to cysteine persulfidation.
(WILEY, 2022-10-17)Post-translational modifications by ubiquitin-like proteins (UBLs) are essential for nearly all cellular processes. Ubiquitin-related modifier 1 (Urm1) is a unique UBL, which plays a key role in tRNA anticodon thiolation ... -
Evaluation of APOBEC3B Recognition Motifs by NMR Reveals Preferred Substrates.
(AMER CHEMICAL SOC, 2018-09-21)APOBEC3B (A3B) deamination activity on ssDNA is considered a contributing factor to tumor heterogeneity and drug resistance in a number of human cancers. Despite its clinical impact, little is known about A3B ssDNA substrate ... -
Exploiting evolutionary steering to induce collateral drug sensitivity in cancer.
(NATURE PORTFOLIO, 2020-04-21)Drug resistance mediated by clonal evolution is arguably the biggest problem in cancer therapy today. However, evolving resistance to one drug may come at a cost of decreased fecundity or increased sensitivity to another ... -
Exploiting Protein Conformational Change to Optimize Adenosine-Derived Inhibitors of HSP70.
(AMER CHEMICAL SOC, 2016-05-26)HSP70 is a molecular chaperone and a key component of the heat-shock response. Because of its proposed importance in oncology, this protein has become a popular target for drug discovery, efforts which have as yet brought ... -
Expression of Mitochondrial Cytochrome C Oxidase Chaperone Gene (COX20) Improves Tolerance to Weak Acid and Oxidative Stress during Yeast Fermentation.
(PUBLIC LIBRARY SCIENCE, 2015-10-01)INTRODUCTION: Saccharomyces cerevisiae is the micro-organism of choice for the conversion of fermentable sugars released by the pre-treatment of lignocellulosic material into bioethanol. Pre-treatment of lignocellulosic ... -
Fragment-based screening identifies molecules targeting the substrate-binding ankyrin repeat domains of tankyrase.
(NATURE PUBLISHING GROUP, 2019-12-13)The PARP enzyme and scaffolding protein tankyrase (TNKS, TNKS2) uses its ankyrin repeat clusters (ARCs) to bind a wide range of proteins and thereby controls diverse cellular functions. A number of these are implicated in ... -
Functional studies of genome architectural proteins CTCF and ZNF143
(Institute of Cancer Research (University Of London), 2021-09-30)The genome architecture and gene transcription are interdependent. The way chromatin is packed within the nucleus controls when and how genes are expressed. A lot of chromatin interacting proteins are involved to ensure ... -
Genome-wide and high-density CRISPR-Cas9 screens identify point mutations in PARP1 causing PARP inhibitor resistance.
(NATURE PUBLISHING GROUP, 2018-05-01)Although PARP inhibitors (PARPi) target homologous recombination defective tumours, drug resistance frequently emerges, often via poorly understood mechanisms. Here, using genome-wide and high-density CRISPR-Cas9 ... -
Genomic and Transcriptomic Determinants of Therapy Resistance and Immune Landscape Evolution during Anti-EGFR Treatment in Colorectal Cancer.
(CELL PRESS, 2019-06-26)Despite biomarker stratification, the anti-EGFR antibody cetuximab is only effective against a subgroup of colorectal cancers (CRCs). This genomic and transcriptomic analysis of the cetuximab resistance landscape in 35 RAS ... -
Heterologous Assembly of Pleomorphic Bacterial Microcompartment Shell Architectures Spanning the Nano- to Microscale.
(WILEY-V C H VERLAG GMBH, 2023-03-18)Many bacteria use protein-based organelles known as bacterial microcompartments (BMCs) to organize and sequester sequential enzymatic reactions. Regardless of their specialized metabolic function, all BMCs are delimited ... -
High Proliferation Rate and a Compromised Spindle Assembly Checkpoint Confers Sensitivity to the MPS1 Inhibitor BOS172722 in Triple-Negative Breast Cancers.
(AMER ASSOC CANCER RESEARCH, 2019-10-01)BOS172722 (CCT289346) is a highly potent, selective, and orally bioavailable inhibitor of spindle assembly checkpoint kinase MPS1. BOS172722 treatment alone induces significant sensitization to death, particularly in highly ... -
High-resolution cryo-EM proteasome structures in drug development.
(INT UNION CRYSTALLOGRAPHY, 2017-06-01)With the recent advances in biological structural electron microscopy (EM), protein structures can now be obtained by cryo-EM and single-particle analysis at resolutions that used to be achievable only by crystallographic ... -
Human Condensin I and II Drive Extensive ATP-Dependent Compaction of Nucleosome-Bound DNA.
(CELL PRESS, 2020-07-02)Structural maintenance of chromosomes (SMC) complexes are essential for genome organization from bacteria to humans, but their mechanisms of action remain poorly understood. Here, we characterize human SMC complexes condensin ... -
Hybrid Gene Origination Creates Human-Virus Chimeric Proteins during Infection.
(CELL PRESS, 2020-06-25)RNA viruses are a major human health threat. The life cycles of many highly pathogenic RNA viruses like influenza A virus (IAV) and Lassa virus depends on host mRNA, because viral polymerases cleave 5'-m7G-capped host ... -
Identification of autophagy-specific cargo and characterization of b-catenin as LC3/GABARAP interacting protein
(Institute of Cancer Research (University Of London), 2023-07-17)Autophagy is an evolutionary conserved eukaryotic degradation system induced under cellular stress conditions in which cellular components, such as damaged organelles, and aggregated proteins sequestrated through lysomal ... -
Identifying and Validating Tankyrase Binders and Substrates: A Candidate Approach.
(Springer New York, 2017-01-01)The poly(ADP-ribose)polymerase (PARP) enzyme tankyrase (TNKS/ARTD5, TNKS2/ARTD6) uses its ankyrin repeat clusters (ARCs) to recognize degenerate peptide motifs in a wide range of proteins, thereby recruiting such proteins ...
