Browsing Structural Biology by title
Now showing items 8-27 of 114
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Achieving In Vivo Target Depletion through the Discovery and Optimization of Benzimidazolone BCL6 Degraders.
(AMER CHEMICAL SOC, 2020-04-23)Deregulation of the transcriptional repressor BCL6 enables tumorigenesis of germinal center B-cells, and hence BCL6 has been proposed as a therapeutic target for the treatment of diffuse large B-cell lymphoma (DLBCL). ... -
ADP-ribosyltransferases, an update on function and nomenclature.
(WILEY, 2021-07-29)ADP-ribosylation, a modification of proteins, nucleic acids, and metabolites, confers broad functions, including roles in stress responses elicited, for example, by DNA damage and viral infection and is involved in intra- ... -
Alternative catalytic residues in the active site of Esco acetyltransferases.
(NATURE PORTFOLIO, 2020-06-17)Cohesin is a protein complex whose core subunits, Smc1, Smc3, Scc1, and SA1/SA2 form a ring-like structure encircling the DNA. Cohesins play a key role in the expression, repair, and segregation of eukaryotic genomes. ... -
An Irreversible Inhibitor of HSP72 that Unexpectedly Targets Lysine-56.
(WILEY-V C H VERLAG GMBH, 2017-03-20)The stress-inducible molecular chaperone, HSP72, is an important therapeutic target in oncology, but inhibiting this protein with small molecules has proven particularly challenging. Validating HSP72 inhibitors in cells ... -
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 ... -
Assessing histone demethylase inhibitors in cells: lessons learned.
(BIOMED CENTRAL LTD, 2017-03-01)BACKGROUND: Histone lysine demethylases (KDMs) are of interest as drug targets due to their regulatory roles in chromatin organization and their tight associations with diseases including cancer and mental disorders. The ... -
AXIN Shapes Tankyrase ARChitecture.
(CELL PRESS, 2016-10-04)The poly(ADP-ribose)polymerase (PARP) Tankyrase uses ankyrin repeat modules to capture substrates via Tankyrase-binding peptide motifs. In this issue of Structure, Eisemann et al. (2016) describe how the signaling protein ... -
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 ... -
A biochemical analysis of human shelterin complexes
(Institute of Cancer Research (University Of London), 2022-08-25)Linear chromosomes present two major challenges, known as the end-replication and end-protection problems. The human shelterin complex is a dynamic assembly of six components, consisting of TRF1, TRF2, RAP1, TIN2, TPP1, ... -
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 ... -
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 ... -
Cell cycle regulation by complex nanomachines.
(WILEY, 2021-06-18)The cell cycle is the essential biological process where one cell replicates its genome and segregates the resulting two copies into the daughter cells during mitosis. Several aspects of this process have fascinated humans ... -
Characterisation of CCT271850, a selective, oral and potent MPS1 inhibitor, used to directly measure in vivo MPS1 inhibition vs therapeutic efficacy.
(NATURE PUBLISHING GROUP, 2017-04-25)BACKGROUND: The main role of the cell cycle is to enable error-free DNA replication, chromosome segregation and cytokinesis. One of the best characterised checkpoint pathways is the spindle assembly checkpoint, which ... -
Characterization of Hedgehog Acyltransferase Inhibitors Identifies a Small Molecule Probe for Hedgehog Signaling by Cancer Cells.
(AMER CHEMICAL SOC, 2016-12-16)The Sonic Hedgehog (Shh) signaling pathway plays a critical role during embryonic development and cancer progression. N-terminal palmitoylation of Shh by Hedgehog acyltransferase (Hhat) is essential for efficient signaling, ... -
Cnn1 inhibits the interactions between the KMN complexes of the yeast kinetochore.
(NATURE PUBLISHING GROUP, 2012-05-06)Kinetochores attach the replicated chromosomes to the mitotic spindle and orchestrate their transmission to the daughter cells. Kinetochore-spindle binding and chromosome segregation are mediated by the multi-copy KNL1(Spc105), ... -
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 ... -
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 ... -
Demonstrating In-Cell Target Engagement Using a Pirin Protein Degradation Probe (CCT367766).
(AMER CHEMICAL SOC, 2018-02-08)Demonstrating intracellular protein target engagement is an essential step in the development and progression of new chemical probes and potential small molecule therapeutics. However, this can be particularly challenging ... -
Discovery and Characterization of a Cryptic Secondary Binding Site in the Molecular Chaperone HSP70.
(MDPI, 2022-01-26)Heat Shock Protein 70s (HSP70s) are key molecular chaperones that are overexpressed in many cancers and often associated with metastasis and poor prognosis. It has proven difficult to develop ATP-competitive, drug-like ... -
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 ...