Browsing Structural Biology by title
Now showing items 86-105 of 115
-
SF3B1 mutations constitute a novel therapeutic target in breast cancer.
(WILEY, 2015-03-01)Mutations in genes encoding proteins involved in RNA splicing have been found to occur at relatively high frequencies in several tumour types including myelodysplastic syndromes, chronic lymphocytic leukaemia, uveal melanoma, ... -
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; ... -
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 ... -
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 ... -
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 ... -
Structural basis for translocation by AddAB helicase-nuclease and its arrest at χ sites.
(NATURE PUBLISHING GROUP, 2014-04-17)In bacterial cells, processing of double-stranded DNA breaks for repair by homologous recombination is dependent upon the recombination hotspot sequence χ (Chi) and is catalysed by either an AddAB- or RecBCD-type ... -
Structural basis of catalytic activation in human splicing.
(NATURE PORTFOLIO, 2023-05-25)Pre-mRNA splicing follows a pathway driven by ATP-dependent RNA helicases. A crucial event of the splicing pathway is the catalytic activation, which takes place at the transition between the activated Bact and the ... -
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 ... -
Structural basis of intron selection by U2 snRNP in the presence of covalent inhibitors
(Springer Science and Business Media LLC, 2021-07-23)<jats:title>Abstract</jats:title><jats:p>Intron selection during the formation of prespliceosomes is a critical event in pre-mRNA splicing. Chemical modulation of intron selection has emerged as a route for cancer therapy. ... -
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 ... -
Structural basis of tankyrase activation by polymerization.
(NATURE PORTFOLIO, 2022-12-01)The poly-ADP-ribosyltransferase tankyrase (TNKS, TNKS2) controls a wide range of disease-relevant cellular processes, including WNT-β-catenin signalling, telomere length maintenance, Hippo signalling, DNA damage repair and ... -
Structural basis of Ty3 retrotransposon integration at RNA Polymerase III-transcribed genes.
(NATURE PORTFOLIO, 2021-11-30)Retrotransposons are endogenous elements that have the ability to mobilise their DNA between different locations in the host genome. The Ty3 retrotransposon integrates with an exquisite specificity in a narrow window ... -
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 ... -
Structural transitions in the GTP cap visualized by cryo-electron microscopy of catalytically inactive microtubules.
(NATL ACAD SCIENCES, 2022-01-11)Microtubules (MTs) are polymers of αβ-tubulin heterodimers that stochastically switch between growth and shrinkage phases. This dynamic instability is critically important for MT function. It is believed that GTP hydrolysis ... -
Structure of human RNA polymerase III.
(NATURE RESEARCH, 2020-12-17)In eukaryotes, RNA Polymerase (Pol) III is specialized for the transcription of tRNAs and other short, untranslated RNAs. Pol III is a determinant of cellular growth and lifespan across eukaryotes. Upregulation of Pol III ... -
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 ... -
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 ... -
Structures of APC/C(Cdh1) with substrates identify Cdh1 and Apc10 as the D-box co-receptor.
(NATURE PUBLISHING GROUP, 2011-02-10)The ubiquitylation of cell-cycle regulatory proteins by the large multimeric anaphase-promoting complex (APC/C) controls sister chromatid segregation and the exit from mitosis. Selection of APC/C targets is achieved through ... -
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 ...
