Browsing Structural Biology by title
Now showing items 63-82 of 115
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Multiparameter Lead Optimization to Give an Oral Checkpoint Kinase 1 (CHK1) Inhibitor Clinical Candidate: (R)-5-((4-((Morpholin-2-ylmethyl)amino)-5-(trifluoromethyl)pyridin-2-yl)amino)pyrazine-2-carbonitrile (CCT245737).
(AMER CHEMICAL SOC, 2016-06-09)Multiparameter optimization of a series of 5-((4-aminopyridin-2-yl)amino)pyrazine-2-carbonitriles resulted in the identification of a potent and selective oral CHK1 preclinical development candidate with in vivo efficacy ... -
Myosin and Actin Filaments in Muscle: Structures and Interactions.
(SPRINGER INTERNATIONAL PUBLISHING AG, 2017-01-01)In the last decade, improvements in electron microscopy and image processing have permitted significantly higher resolutions to be achieved (sometimes <1 nm) when studying isolated actin and myosin filaments. In the case ... -
Nanostructures from Synthetic Genetic Polymers.
(WILEY-V C H VERLAG GMBH, 2016-06-16)Nanoscale objects of increasing complexity can be constructed from DNA or RNA. However, the scope of potential applications could be enhanced by expanding beyond the moderate chemical diversity of natural nucleic acids. ... -
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 ... -
Nse5/6 is a negative regulator of the ATPase activity of the Smc5/6 complex.
(OXFORD UNIV PRESS, 2021-05-07)The multi-component Smc5/6 complex plays a critical role in the resolution of recombination intermediates formed during mitosis and meiosis, and in the cellular response to replication stress. Using recombinant proteins, ... -
Origin licensing requires ATP binding and hydrolysis by the MCM replicative helicase.
(CELL PRESS, 2014-09-04)Loading of the six related Minichromosome Maintenance (MCM) proteins as head-to-head double hexamers during DNA replication origin licensing is crucial for ensuring once-per-cell-cycle DNA replication in eukaryotic cells. ... -
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 ... -
Prereplicative complexes assembled in vitro support origin-dependent and independent DNA replication.
(WILEY-BLACKWELL, 2014-03-18)Eukaryotic DNA replication initiates from multiple replication origins. To ensure each origin fires just once per cell cycle, initiation is divided into two biochemically discrete steps: the Mcm2-7 helicase is first loaded ... -
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 ... -
Rapid Discovery of Pyrido[3,4-d]pyrimidine Inhibitors of Monopolar Spindle Kinase 1 (MPS1) Using a Structure-Based Hybridization Approach.
(AMER CHEMICAL SOC, 2016-04-28)Monopolar spindle 1 (MPS1) plays a central role in the transition of cells from metaphase to anaphase and is one of the main components of the spindle assembly checkpoint. Chromosomally unstable cancer cells rely heavily ... -
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 ... -
Reconstitution of the destruction complex defines roles of AXIN polymers and APC in β-catenin capture, phosphorylation, and ubiquitylation.
(CELL PRESS, 2021-08-19)The Wnt/β-catenin pathway is a highly conserved, frequently mutated developmental and cancer pathway. Its output is defined mainly by β-catenin's phosphorylation- and ubiquitylation-dependent proteasomal degradation, ... -
Redox requirements for ubiquitin-like urmylation of Ahp1, a 2-Cys peroxiredoxin from yeast.
(ELSEVIER, 2020-02-01)The yeast peroxiredoxin Ahp1, like related anti-oxidant enzymes in other species, undergoes urmylation, a lysine-directed conjugation to ubiquitin-like modifier Urm1. Ahp1 assembles into a homodimer that detoxifies peroxides ... -
Redox Signaling by the RNA Polymerase III TFIIB-Related Factor Brf2.
(CELL PRESS, 2015-12-03)TFIIB-related factor 2 (Brf2) is a member of the family of TFIIB-like core transcription factors. Brf2 recruits RNA polymerase (Pol) III to type III gene-external promoters, including the U6 spliceosomal RNA and selenocysteine ... -
Regulation of Protein Interactions by Mps One Binder (MOB1) Phosphorylation.
(AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC, 2017-06-01)MOB1 is a multifunctional protein best characterized for its integrative role in regulating Hippo and NDR pathway signaling in metazoans and the Mitotic Exit Network in yeast. Human MOB1 binds both the upstream kinases ... -
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 ... -
Relaxed and active thin filament structures; a new structural basis for the regulatory mechanism.
(ACADEMIC PRESS INC ELSEVIER SCIENCE, 2017-03-01)The structures of muscle thin filaments reconstituted using skeletal actin and cardiac troponin and tropomyosin have been determined with and without bound Ca2+ using electron microscopy and reference-free single particle ... -
RET recognition of GDNF-GFRα1 ligand by a composite binding site promotes membrane-proximal self-association.
(CELL PRESS, 2014-09-25)The RET receptor tyrosine kinase is essential to vertebrate development and implicated in multiple human diseases. RET binds a cell surface bipartite ligand comprising a GDNF family ligand and a GFRα coreceptor, resulting ... -
REVEL: An Ensemble Method for Predicting the Pathogenicity of Rare Missense Variants.
(CELL PRESS, 2016-10-06)The vast majority of coding variants are rare, and assessment of the contribution of rare variants to complex traits is hampered by low statistical power and limited functional data. Improved methods for predicting the ...
