Browsing Structural Biology by issue date
Now showing items 41-60 of 114
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Structure-Enabled Discovery of a Stapled Peptide Inhibitor to Target the Oncogenic Transcriptional Repressor TLE1.
(WILEY-V C H VERLAG GMBH, 2017-07-18)TLE1 is an oncogenic transcriptional co-repressor that exerts its repressive effects through binding of transcription factors. Inhibition of this protein-protein interaction represents a putative cancer target, but no ... -
Molecular mechanisms of Bdp1 in TFIIIB assembly and RNA polymerase III transcription initiation.
(NATURE PUBLISHING GROUP, 2017-07-25)Initiation of gene transcription by RNA polymerase (Pol) III requires the activity of TFIIIB, a complex formed by Brf1 (or Brf2), TBP (TATA-binding protein), and Bdp1. TFIIIB is required for recruitment of Pol III and to ... -
RNA polymerase I, bending the rules?
(WILEY, 2017-09-15)Transcription initiation is one of the key regulatory steps in expressing the genetic information encoded in the DNA. Mechanisms of RNA Pol II transcription have been extensively studied, whereas the structural basis of ... -
Visualizing the complex functions and mechanisms of the anaphase promoting complex/cyclosome (APC/C).
(ROYAL SOC, 2017-11-01)The anaphase promoting complex or cyclosome (APC/C) is a large multi-subunit E3 ubiquitin ligase that orchestrates cell cycle progression by mediating the degradation of important cell cycle regulators. During the two ... -
Structure-based drug design: aiming for a perfect fit.
(PORTLAND PRESS LTD, 2017-11-08)Knowledge of the three-dimensional structure of therapeutically relevant targets has informed drug discovery since the first protein structures were determined using X-ray crystallography in the 1950s and 1960s. In this ... -
Regulation of Wnt/β-catenin signalling by tankyrase-dependent poly(ADP-ribosyl)ation and scaffolding.
(WILEY, 2017-12-01)UNLABELLED: The Wnt/β-catenin signalling pathway is pivotal for stem cell function and the control of cellular differentiation, both during embryonic development and tissue homeostasis in adults. Its activity is carefully ... -
New tricks for an old dog: Brf2-dependent RNA Polymerase III transcription in oxidative stress and cancer.
(TAYLOR & FRANCIS INC, 2018-01-01)Here, we discuss the role of Brf2, an RNA Polymerase III core transcription factor, as a master switch of the oxidative stress response. We highlight the interplay of Brf2 with the Nrf2/Keap1 pathway, as well as the role ... -
Structural basis of RNA polymerase III transcription initiation.
(NATURE PORTFOLIO, 2018-01-17)RNA polymerase (Pol) III transcribes essential non-coding RNAs, including the entire pool of transfer RNAs, the 5S ribosomal RNA and the U6 spliceosomal RNA, and is often deregulated in cancer cells. The initiation of gene ... -
RavN is a member of a previously unrecognized group of Legionella pneumophila E3 ubiquitin ligases.
(PUBLIC LIBRARY SCIENCE, 2018-02-01)The eukaryotic ubiquitylation machinery catalyzes the covalent attachment of the small protein modifier ubiquitin to cellular target proteins in order to alter their fate. Microbial pathogens exploit this post-translational ... -
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 ... -
Patient-derived organoids model treatment response of metastatic gastrointestinal cancers.
(AMER ASSOC ADVANCEMENT SCIENCE, 2018-02-23)Patient-derived organoids (PDOs) have recently emerged as robust preclinical models; however, their potential to predict clinical outcomes in patients has remained unclear. We report on a living biobank of PDOs from ... -
MIR21 Drives Resistance to Heat Shock Protein 90 Inhibition in Cholangiocarcinoma.
(W B SAUNDERS CO-ELSEVIER INC, 2018-03-01)BACKGROUND & AIMS: Cholangiocarcinomas (CCA) are resistant to chemotherapy, so new therapeutic agents are needed. We performed a screen to identify small-molecule compounds that are active against CCAs. Levels of microRNA ... -
Structural rearrangements of the RNA polymerase III machinery during tRNA transcription initiation.
(ELSEVIER SCIENCE BV, 2018-04-01)RNA polymerase III catalyses the synthesis of tRNAs in eukaryotic organisms. Through combined biochemical and structural characterisation, multiple auxiliary factors have been identified alongside RNA Polymerase III as ... -
Mechanism of selective recruitment of RNA polymerases II and III to snRNA gene promoters.
(COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT, 2018-05-01)RNA polymerase II (Pol II) small nuclear RNA (snRNA) promoters and type 3 Pol III promoters have highly similar structures; both contain an interchangeable enhancer and "proximal sequence element" (PSE), which recruits the ... -
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 ... -
Mechanism for remodelling of the cell cycle checkpoint protein MAD2 by the ATPase TRIP13.
(NATURE PUBLISHING GROUP, 2018-07-12)The maintenance of genome stability during mitosis is coordinated by the spindle assembly checkpoint (SAC) through its effector the mitotic checkpoint complex (MCC), an inhibitor of the anaphase-promoting complex (APC/C, ... -
Synthesis and profiling of a 3-aminopyridin-2-one-based kinase targeted fragment library: Identification of 3-amino-5-(pyridin-4-yl)pyridin-2(1H)-one scaffold for monopolar spindle 1 (MPS1) and Aurora kinases inhibition.
(PERGAMON-ELSEVIER SCIENCE LTD, 2018-07-15)Screening a 3-aminopyridin-2-one based fragment library against a 26-kinase panel representative of the human kinome identified 3-amino-5-(1-methyl-1H-pyrazol-4-yl)pyridin-2(1H)-one (2) and 3-amino-5-(pyridin-4-yl)pyridi ... -
Structural Basis for Auto-Inhibition of the NDR1 Kinase Domain by an Atypically Long Activation Segment.
(CELL PRESS, 2018-08-07)The human NDR family kinases control diverse aspects of cell growth, and are regulated through phosphorylation and association with scaffolds such as MOB1. Here, we report the crystal structure of the human NDR1 kinase ... -
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 ... -
Privileged Structures and Polypharmacology within and between Protein Families.
(AMER CHEMICAL SOC, 2018-12-13)Polypharmacology is often a key contributor to the efficacy of a drug, but is also a potential risk. We investigated two hits discovered via a cell-based phenotypic screen, the CDK9 inhibitor CCT250006 (1) and the pirin ...