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Now showing items 3885-3904 of 4595
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Structural basis of N-Myc binding by Aurora-A and its destabilization by kinase inhibitors.
(NATL ACAD SCIENCES, 2016-11-29)Myc family proteins promote cancer by inducing widespread changes in gene expression. Their rapid turnover by the ubiquitin-proteasome pathway is regulated through phosphorylation of Myc Box I and ubiquitination by the E3 ... -
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 ... -
A structural biology community assessment of AlphaFold2 applications.
(Springer Science and Business Media LLC, 2022-11-01)Most proteins fold into 3D structures that determine how they function and orchestrate the biological processes of the cell. Recent developments in computational methods for protein structure predictions have reached the ... -
Structural investigation of NTC and of the coupling between splicing and polyadenylation
(Institute of Cancer Research (University Of London), 2022-10-31)This PhD thesis is composed of two parts. The first and foremost part describes the reconstitution, isolation and analysis of human complexes involved in the coupling between splicing and polyadenylation, with a special ... -
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 ... -
Structural variants shape driver combinations and outcomes in pediatric high-grade glioma.
(OXFORD UNIV PRESS INC, 2022-06-01)We analyzed the contributions of structural variants (SVs) to gliomagenesis across 179 pediatric high-grade gliomas (pHGGs). The most recurrent SVs targeted MYC isoforms and receptor tyrosine kinases (RTKs), including an ... -
The structure and mechanism of the EXD2 nuclease in DNA repair
(Institute of Cancer Research (University Of London), 2023-06-09)DNA double strand breaks (DSBs) are one of the most toxic DNA lesions. They can jeopardise stability of the genome and lead to cancer development. There are two main pathways of DSB repair: homologous recombination (HR) ... -
Structure enabled design of BAZ2-ICR, a chemical probe targeting the bromodomains of BAZ2A and BAZ2B.
(AMER CHEMICAL SOC, 2015-03-12)The bromodomain containing proteins BAZ2A/B play essential roles in chromatin remodeling and regulation of noncoding RNAs. We present the structure based discovery of a potent, selective, and cell active inhibitor 13 ... -
Structure of a nucleosome-bound MuvB transcription factor complex reveals DNA remodelling.
(NATURE PORTFOLIO, 2022-08-29)Genes encoding the core cell cycle machinery are transcriptionally regulated by the MuvB family of protein complexes in a cell cycle-specific manner. Complexes of MuvB with the transcription factors B-MYB and FOXM1 activate ... -
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 of the human RAD17-RFC clamp loader and 9-1-1 checkpoint clamp bound to a dsDNA-ssDNA junction.
(OXFORD UNIV PRESS, 2022-08-12)The RAD9-RAD1-HUS1 (9-1-1) clamp forms one half of the DNA damage checkpoint system that signals the presence of substantial regions of single-stranded DNA arising from replication fork collapse or resection of DNA double ... -
Structure-based design of selective and potent G quadruplex-mediated telomerase inhibitors
(2001-04-24)The telomerase enzyme is a potential therapeutic target in many human cancers. A series of potent inhibitors has been designed by computer modeling, which exploit the unique structural features of quadruplex DNA, These ... -
Structure-based development of new RAS-effector inhibitors from a combination of active and inactive RAS-binding compounds.
(NATL ACAD SCIENCES, 2019-02-12)The RAS gene family is frequently mutated in human cancers, and the quest for compounds that bind to mutant RAS remains a major goal, as it also does for inhibitors of protein-protein interactions. We have refined ... -
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-Based Optimization of Potent, Selective, and Orally Bioavailable CDK8 Inhibitors Discovered by High-Throughput Screening.
(AMER CHEMICAL SOC, 2016-10-27)The mediator complex-associated cyclin dependent kinase CDK8 regulates β-catenin-dependent transcription following activation of WNT signaling. Multiple lines of evidence suggest CDK8 may act as an oncogene in the development ... -
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 ... -
Structure-guided design of purine-based probes for selective Nek2 inhibition
(2017)Nek2 (NIMA-related kinase 2) is a cell cycle-dependent serine/threonine protein kinase that regulates centrosome separation at the onset of mitosis. Overexpression of Nek2 is common in human cancers and suppression can ...
