Browsing Structural Biology by issue date
Now showing items 61-80 of 114
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Roles of Elongator Dependent tRNA Modification Pathways in Neurodegeneration and Cancer.
(MDPI, 2018-12-28)Transfer RNA (tRNA) is subject to a multitude of posttranscriptional modifications which can profoundly impact its functionality as the essential adaptor molecule in messenger RNA (mRNA) translation. Therefore, dynamic ... -
Binding to an Unusual Inactive Kinase Conformation by Highly Selective Inhibitors of Inositol-Requiring Enzyme 1α Kinase-Endoribonuclease.
(AMER CHEMICAL SOC, 2019-02-19)A series of imidazo[1,2- b]pyridazin-8-amine kinase inhibitors were discovered to allosterically inhibit the endoribonuclease function of the dual kinase-endoribonuclease inositol-requiring enzyme 1α (IRE1α), a key component ... -
CEA expression heterogeneity and plasticity confer resistance to the CEA-targeting bispecific immunotherapy antibody cibisatamab (CEA-TCB) in patient-derived colorectal cancer organoids.
(BMJ PUBLISHING GROUP, 2019-03-21)BACKGROUND: The T cell bispecific antibody cibisatamab (CEA-TCB) binds Carcino-Embryonic Antigen (CEA) on cancer cells and CD3 on T cells, which triggers T cell killing of cancer cell lines expressing moderate to high ... -
Solution NMR assignment of the ARC4 domain of human tankyrase 2.
(SPRINGER, 2019-04-15)Tankyrases are poly(ADP-ribose)polymerases (PARPs) which recognize their substrates via their ankyrin repeat cluster (ARC) domains. The human tankyrases (TNKS/TNKS2) contain five ARCs in their extensive N-terminal region; ... -
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 ... -
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 ... -
Three-dimensional structure of the basketweave Z-band in midshipman fish sonic muscle.
(NATL ACAD SCIENCES, 2019-07-30)Striated muscle enables movement in all animals by the contraction of myriads of sarcomeres joined end to end by the Z-bands. The contraction is due to tension generated in each sarcomere between overlapping arrays of actin ... -
Structural basis of Cullin 2 RING E3 ligase regulation by the COP9 signalosome.
(NATURE RESEARCH, 2019-08-23)Cullin-Ring E3 Ligases (CRLs) regulate a multitude of cellular pathways through specific substrate receptors. The COP9 signalosome (CSN) deactivates CRLs by removing NEDD8 from activated Cullins. Here we present structures ... -
C8-substituted pyrido[3,4-d]pyrimidin-4(3H)-ones: Studies towards the identification of potent, cell penetrant Jumonji C domain containing histone lysine demethylase 4 subfamily (KDM4) inhibitors, compound profiling in cell-based target engagement assays.
(ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER, 2019-09-01)Residues in the histone substrate binding sites that differ between the KDM4 and KDM5 subfamilies were identified. Subsequently, a C8-substituted pyrido[3,4-d]pyrimidin-4(3H)-one series was designed to rationally exploit ... -
Structural and functional characterisation of human RNA helicase DHX8 provides insights into the mechanism of RNA-stimulated ADP release.
(PORTLAND PRESS LTD, 2019-09-13)DHX8 is a crucial DEAH-box RNA helicase involved in splicing and required for the release of mature mRNA from the spliceosome. Here, we report the biochemical characterisation of full-length human DHX8 and the catalytically ... -
The Interacting Head Motif Structure Does Not Explain the X-Ray Diffraction Patterns in Relaxed Vertebrate (Bony Fish) Skeletal Muscle and Insect (Lethocerus) Flight Muscle.
(MDPI, 2019-09-14)Unlike electron microscopy, which can achieve very high resolution but to date can only be used to study static structures, time-resolved X-ray diffraction from contracting muscles can, in principle, be used to follow the ... -
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 ... -
A Role for COX20 in Tolerance to Oxidative Stress and Programmed Cell Death in Saccharomyces cerevisiae.
(MDPI, 2019-11-18)Industrial production of bioethanol from lignocellulosic materials (LCM's) is reliant on a microorganism being tolerant to the stresses inherent to fermentation. Previous work has highlighted the importance of a cytochrome ... -
Structural and functional characterization of the human and yeast TFIIIC complex
(Institute of Cancer Research (University Of London), 2019-11-30)TFIIIC is one of the conserved transcription factors required for RNA Polymerase (Pol) III transcription, which transcribes DNA into untranslated RNAs, such as tRNAs. However, TFIIIC's mechanistic role in Pol III regulation ... -
Fragment-based screening identifies molecules targeting the substrate-binding ankyrin repeat domains of tankyrase.
(NATURE PORTFOLIO, 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 ... -
Architecture of the chromatin remodeler RSC and insights into its nucleosome engagement.
(ELIFE SCIENCES PUBLICATIONS LTD, 2019-12-30)Eukaryotic DNA is packaged into nucleosome arrays, which are repositioned by chromatin remodeling complexes to control DNA accessibility. The Saccharomyces cerevisiae RSC (Remodeling the Structure of Chromatin) complex, a ... -
Combining large scale in silico analysis with fragment screening to identify novel, ligandable secondary sites in cancer-associated proteins
(Institute of Cancer Research (University Of London), 2020-01-31)Proteins often have multiple binding sites involved in interactions with other molecules. The majority of currently approved drugs bind a protein's primary site, the major functional site in the protein. Targeting the ... -
Redox requirements for ubiquitin-like urmylation of Ahp1, a 2-Cys peroxiredoxin from yeast.
(ELSEVIER, 2020-02-01)The yeast peroxiredoxin Ahp1, like related anti-oxidant enzymes in other species, undergoes urmylation, a lysine-directed conjugation to ubiquitin-like modifier Urm1. Ahp1 assembles into a homodimer that detoxifies peroxides ... -
Cryo-EM structures of the XPF-ERCC1 endonuclease reveal how DNA-junction engagement disrupts an auto-inhibited conformation.
(NATURE PUBLISHING GROUP, 2020-02-28)The structure-specific endonuclease XPF-ERCC1 participates in multiple DNA damage repair pathways including nucleotide excision repair (NER) and inter-strand crosslink repair (ICLR). How XPF-ERCC1 is catalytically activated ... -
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 ...