Browsing Structural Biology by title
Now showing items 48-67 of 115
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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 ... -
An integrated model for termination of RNA polymerase III transcription.
(American Association for the Advancement of Science (AAAS), 2022-07-15)RNA polymerase III (RNAPIII) synthesizes essential and abundant noncoding RNAs such as transfer RNAs. Controlling RNAPIII span of activity by accurate and efficient termination is a challenging necessity to ensure robust ... -
Into Deep Water: Optimizing BCL6 Inhibitors by Growing into a Solvated Pocket.
(AMER CHEMICAL SOC, 2021-12-09)We describe the optimization of modestly active starting points to potent inhibitors of BCL6 by growing into a subpocket, which was occupied by a network of five stably bound water molecules. Identifying potent inhibitors ... -
Investigating the phosphinic acid tripeptide mimetic DG013A as a tool compound inhibitor of the M1-aminopeptidase ERAP1.
(PERGAMON-ELSEVIER SCIENCE LTD, 2021-06-15)ERAP1 is a zinc-dependent M1-aminopeptidase that trims lipophilic amino acids from the N-terminus of peptides. Owing to its importance in the processing of antigens and regulation of the adaptive immune response, dysregulation ... -
Large Stokes shift fluorescence activation in an RNA aptamer by intermolecular proton transfer to guanine.
(NATURE RESEARCH, 2021-06-10)Fluorogenic RNA aptamers are synthetic functional RNAs that specifically bind and activate conditional fluorophores. The Chili RNA aptamer mimics large Stokes shift fluorescent proteins and exhibits high affinity for ... -
MCPH1 inhibits Condensin II during interphase by regulating its SMC2-Kleisin interface.
(eLife Sciences Publications, Ltd, 2021-12-01)Dramatic change in chromosomal DNA morphology between interphase and mitosis is a defining features of the eukaryotic cell cycle. Two types of enzymes, namely cohesin and condensin confer the topology of chromosomal DNA ... -
Mechanism for remodelling of the cell cycle checkpoint protein MAD2 by the ATPase TRIP13.
(NATURE PUBLISHING GROUP, 2018-07-12)The maintenance of genome stability during mitosis is coordinated by the spindle assembly checkpoint (SAC) through its effector the mitotic checkpoint complex (MCC), an inhibitor of the anaphase-promoting complex (APC/C, ... -
Mechanism of selective recruitment of RNA polymerases II and III to snRNA gene promoters.
(COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT, 2018-05-01)RNA polymerase II (Pol II) small nuclear RNA (snRNA) promoters and type 3 Pol III promoters have highly similar structures; both contain an interchangeable enhancer and "proximal sequence element" (PSE), which recruits the ... -
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 ...
