Browsing Structural Biology by title
Now showing items 1-20 of 103
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2,8-Disubstituted-1,6-Naphthyridines and 4,6-Disubstituted-Isoquinolines with Potent, Selective Affinity for CDK8/19.
(2016-06)We demonstrate a designed scaffold-hop approach to the discovery of 2,8-disubstituted-1,6-naphthyridine- and 4,6-disubstituted-isoquinoline-based dual CDK8/19 ligands. Optimized compounds in both series exhibited rapid ... -
8-Substituted Pyrido[3,4-d]pyrimidin-4(3H)-one Derivatives As Potent, Cell Permeable, KDM4 (JMJD2) and KDM5 (JARID1) Histone Lysine Demethylase Inhibitors.
(2016-02)We report the discovery of N-substituted 4-(pyridin-2-yl)thiazole-2-amine derivatives and their subsequent optimization, guided by structure-based design, to give 8-(1H-pyrazol-3-yl)pyrido[3,4-d]pyrimidin-4(3H)-ones, a ... -
A closed conformation of the Caenorhabditis elegans separase-securin complex.
(2016-04-13)The protease separase plays a key role in sister chromatid disjunction and centriole disengagement. To maintain genomic stability, separase activity is strictly regulated by binding of an inhibitory protein, securin. Despite ... -
A commercial antibody to the human condensin II subunit NCAPH2 cross-reacts with a SWI/SNF complex component
(2021-01-13)Condensin complexes compact and disentangle chromosomes in preparation for cell division. Commercially available antibodies raised against condensin subunits have been widely used to characterise their cellular interactome. ... -
A commercial antibody to the human condensin II subunit NCAPH2 cross-reacts with a SWI/SNF complex component.
(2021-01-13)Condensin complexes compact and disentangle chromosomes in preparation for cell division. Commercially available antibodies raised against condensin subunits have been widely used to characterise their cellular interactome. ... -
A fragment-based approach applied to a highly flexible target: Insights and challenges towards the inhibition of HSP70 isoforms.
(2016-10-06)The heat shock protein 70s (HSP70s) are molecular chaperones implicated in many cancers and of significant interest as targets for novel cancer therapies. Several HSP70 inhibitors have been reported, but because the majority ... -
A unique binding mode of Nek2A to the APC/C allows its ubiquitination during prometaphase.
(2020-06)The anaphase-promoting complex (APC/C) is the key E3 ubiquitin ligase which directs mitotic progression and exit by catalysing the sequential ubiquitination of specific substrates. The activity of the APC/C in mitosis is ... -
Achieving In Vivo Target Depletion through the Discovery and Optimization of Benzimidazolone BCL6 Degraders.
(2020-04-10)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.
(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.
(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.
(2017-03)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.
(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.
(2017-01)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.
(2016-10)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.
(2019-03-05)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.
(2019-09)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 ... -
Calmodulin-independent, agonistic properties of a peptide containing the calmodulin binding site of estrogen receptor alpha
(2007-03-30)Calmodulin (CaM) contributes to estrogen receptor alpha (ER)-mediated transcription. In order to study the underlying mechanisms, we synthesized a peptide including the CaM binding site: ERalpha17p (P(295)-T(311)). This ... -
CEA expression heterogeneity and plasticity confer resistance to the CEA-targeting bispecific immunotherapy antibody cibisatamab (CEA-TCB) in patient-derived colorectal cancer organoids.
(2019-04-15)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 levels ... -
Cell cycle regulation by complex nanomachines.
(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 ...
