Browsing Structural Biology by title
Now showing items 57-76 of 118
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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 ... -
MOB1 Mediated Phospho-recognition in the Core Mammalian Hippo Pathway.
(AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC, 2017-06-01)The Hippo tumor suppressor pathway regulates organ size and tissue homoeostasis in response to diverse signaling inputs. The core of the pathway consists of a short kinase cascade: MST1 and MST2 phosphorylate and activate ... -
Molecular basis for the bifunctional Uba4-Urm1 sulfur-relay system in tRNA thiolation and ubiquitin-like conjugation.
(WILEY, 2020-10-01)The chemical modification of tRNA bases by sulfur is crucial to tune translation and to optimize protein synthesis. In eukaryotes, the ubiquitin-related modifier 1 (Urm1) pathway is responsible for the synthesis of 2-thiolated ... -
Molecular basis of APC/C regulation by the spindle assembly checkpoint.
(NATURE PUBLISHING GROUP, 2016-08-25)In the dividing eukaryotic cell, the spindle assembly checkpoint (SAC) ensures that each daughter cell inherits an identical set of chromosomes. The SAC coordinates the correct attachment of sister chromatid kinetochores ... -
Molecular mechanism of APC/C activation by mitotic phosphorylation.
(NATURE PUBLISHING GROUP, 2016-05-12)In eukaryotes, the anaphase-promoting complex (APC/C, also known as the cyclosome) regulates the ubiquitin-dependent proteolysis of specific cell-cycle proteins to coordinate chromosome segregation in mitosis and entry ... -
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 ... -
Molecular mechanisms of human IRE1 activation through dimerization and ligand binding.
(IMPACT JOURNALS LLC, 2015-05-30)IRE1 transduces the unfolded protein response by splicing XBP1 through its C-terminal cytoplasmic kinase-RNase region. IRE1 autophosphorylation is coupled to RNase activity through formation of a back-to-back dimer, although ... -
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, ...