Browsing Structural Biology by title
Now showing items 91-110 of 114
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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 ... -
Synthesis of a Ribose-Incorporating Medium Ring Scaffold via a Challenging Ring-Closing Metathesis Reaction.
(WILEY-V C H VERLAG GMBH, 2016-09-01)A practical synthesis of a novel oxabicyclo[6.2.1]undecenetriol useful as a medicinal chemistry scaffold has been developed starting from l-ribose. The sequence involves an oxidation/Grignard addition sequence and a ... -
Tankyrase Requires SAM Domain-Dependent Polymerization to Support Wnt-β-Catenin Signaling.
(CELL PRESS, 2016-08-04)The poly(ADP-ribose) polymerase (PARP) Tankyrase (TNKS and TNKS2) is paramount to Wnt-β-catenin signaling and a promising therapeutic target in Wnt-dependent cancers. The pool of active β-catenin is normally limited by ... -
Targeted therapy for LIMD1-deficient non-small cell lung cancer subtypes.
(SPRINGERNATURE, 2021-11-11)An early event in lung oncogenesis is loss of the tumour suppressor gene LIMD1 (LIM domains containing 1); this encodes a scaffold protein, which suppresses tumorigenesis via a number of different mechanisms. Approximately ... -
The discovery of potent ribosomal S6 kinase inhibitors by high-throughput screening and structure-guided drug design.
(IMPACT JOURNALS LLC, 2013-08-25)The ribosomal P70 S6 kinases play a crucial role in PI3K/mTOR regulated signalling pathways and are therefore potential targets for the treatment of a variety of diseases including diabetes and cancer. In this study we ... -
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 ... -
Three-dimensional structure of recombinant type 1 inositol 1,4,5-trisphosphate receptor.
(PORTLAND PRESS LTD, 2010-05-27)IP3Rs (inositol 1,4,5-trisphosphate receptors) are the intracellular channels that mediate release of Ca2+ from the endoplasmic reticulum in response to the many stimuli that evoke Ins(1,4,5)P3 formation. We characterized ...