Browsing Structural Biology by issue date
Now showing items 21-40 of 114
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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. ... -
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 ... -
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 ... -
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 ... -
Inhibition of mTOR-kinase destabilizes MYCN and is a potential therapy for MYCN-dependent tumors.
(IMPACT JOURNALS LLC, 2016-09-06)MYC oncoproteins deliver a potent oncogenic stimulus in several human cancers, making them major targets for drug development, but efforts to deliver clinically practical therapeutics have not yet been realized. In childhood ... -
AXIN Shapes Tankyrase ARChitecture.
(CELL PRESS, 2016-10-04)The poly(ADP-ribose)polymerase (PARP) Tankyrase uses ankyrin repeat modules to capture substrates via Tankyrase-binding peptide motifs. In this issue of Structure, Eisemann et al. (2016) describe how the signaling protein ... -
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 ... -
A fragment-based approach applied to a highly flexible target: Insights and challenges towards the inhibition of HSP70 isoforms.
(NATURE PORTFOLIO, 2016-10-06)The heat shock protein 70s (HSP70s) are molecular chaperones implicated in many cancers and of significant interest as targets for novel cancer therapies. Several HSP70 inhibitors have been reported, but because the majority ... -
Characterization of Hedgehog Acyltransferase Inhibitors Identifies a Small Molecule Probe for Hedgehog Signaling by Cancer Cells.
(AMER CHEMICAL SOC, 2016-12-16)The Sonic Hedgehog (Shh) signaling pathway plays a critical role during embryonic development and cancer progression. N-terminal palmitoylation of Shh by Hedgehog acyltransferase (Hhat) is essential for efficient signaling, ... -
Utilizing Functional Genomics Screening to Identify Potentially Novel Drug Targets in Cancer Cell Spheroid Cultures.
(JOURNAL OF VISUALIZED EXPERIMENTS, 2016-12-26)The identification of functional driver events in cancer is central to furthering our understanding of cancer biology and indispensable for the discovery of the next generation of novel drug targets. It is becoming apparent ... -
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 ... -
Identifying and Validating Tankyrase Binders and Substrates: A Candidate Approach.
(Springer New York, 2017-01-01)The poly(ADP-ribose)polymerase (PARP) enzyme tankyrase (TNKS/ARTD5, TNKS2/ARTD6) uses its ankyrin repeat clusters (ARCs) to recognize degenerate peptide motifs in a wide range of proteins, thereby recruiting such proteins ... -
Discovery of a Chemical Probe Bisamide (CCT251236): An Orally Bioavailable Efficacious Pirin Ligand from a Heat Shock Transcription Factor 1 (HSF1) Phenotypic Screen.
(AMER CHEMICAL SOC, 2017-01-12)Phenotypic screens, which focus on measuring and quantifying discrete cellular changes rather than affinity for individual recombinant proteins, have recently attracted renewed interest as an efficient strategy for drug ... -
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 ... -
Assessing histone demethylase inhibitors in cells: lessons learned.
(BIOMED CENTRAL LTD, 2017-03-01)BACKGROUND: Histone lysine demethylases (KDMs) are of interest as drug targets due to their regulatory roles in chromatin organization and their tight associations with diseases including cancer and mental disorders. The ... -
An Irreversible Inhibitor of HSP72 that Unexpectedly Targets Lysine-56.
(WILEY-V C H VERLAG GMBH, 2017-03-20)The stress-inducible molecular chaperone, HSP72, is an important therapeutic target in oncology, but inhibiting this protein with small molecules has proven particularly challenging. Validating HSP72 inhibitors in cells ... -
Characterisation of CCT271850, a selective, oral and potent MPS1 inhibitor, used to directly measure in vivo MPS1 inhibition vs therapeutic efficacy.
(NATURE PUBLISHING GROUP, 2017-04-25)BACKGROUND: The main role of the cell cycle is to enable error-free DNA replication, chromosome segregation and cytokinesis. One of the best characterised checkpoint pathways is the spindle assembly checkpoint, which ... -
High-resolution cryo-EM proteasome structures in drug development.
(INT UNION CRYSTALLOGRAPHY, 2017-06-01)With the recent advances in biological structural electron microscopy (EM), protein structures can now be obtained by cryo-EM and single-particle analysis at resolutions that used to be achievable only by crystallographic ... -
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 ... -
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 ...