Browsing Structural Biology by title
Now showing items 37-56 of 115
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Fragment-based screening identifies molecules targeting the substrate-binding ankyrin repeat domains of tankyrase.
(NATURE PUBLISHING GROUP, 2019-12-13)The PARP enzyme and scaffolding protein tankyrase (TNKS, TNKS2) uses its ankyrin repeat clusters (ARCs) to bind a wide range of proteins and thereby controls diverse cellular functions. A number of these are implicated in ... -
Functional studies of genome architectural proteins CTCF and ZNF143
(Institute of Cancer Research (University Of London), 2021-09-30)The genome architecture and gene transcription are interdependent. The way chromatin is packed within the nucleus controls when and how genes are expressed. A lot of chromatin interacting proteins are involved to ensure ... -
Genome-wide and high-density CRISPR-Cas9 screens identify point mutations in PARP1 causing PARP inhibitor resistance.
(NATURE PUBLISHING GROUP, 2018-05-01)Although PARP inhibitors (PARPi) target homologous recombination defective tumours, drug resistance frequently emerges, often via poorly understood mechanisms. Here, using genome-wide and high-density CRISPR-Cas9 ... -
Genomic and Transcriptomic Determinants of Therapy Resistance and Immune Landscape Evolution during Anti-EGFR Treatment in Colorectal Cancer.
(CELL PRESS, 2019-06-26)Despite biomarker stratification, the anti-EGFR antibody cetuximab is only effective against a subgroup of colorectal cancers (CRCs). This genomic and transcriptomic analysis of the cetuximab resistance landscape in 35 RAS ... -
Heterologous Assembly of Pleomorphic Bacterial Microcompartment Shell Architectures Spanning the Nano- to Microscale.
(WILEY-V C H VERLAG GMBH, 2023-03-18)Many bacteria use protein-based organelles known as bacterial microcompartments (BMCs) to organize and sequester sequential enzymatic reactions. Regardless of their specialized metabolic function, all BMCs are delimited ... -
High Proliferation Rate and a Compromised Spindle Assembly Checkpoint Confers Sensitivity to the MPS1 Inhibitor BOS172722 in Triple-Negative Breast Cancers.
(AMER ASSOC CANCER RESEARCH, 2019-10-01)BOS172722 (CCT289346) is a highly potent, selective, and orally bioavailable inhibitor of spindle assembly checkpoint kinase MPS1. BOS172722 treatment alone induces significant sensitization to death, particularly in highly ... -
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 ... -
Human Condensin I and II Drive Extensive ATP-Dependent Compaction of Nucleosome-Bound DNA.
(CELL PRESS, 2020-07-02)Structural maintenance of chromosomes (SMC) complexes are essential for genome organization from bacteria to humans, but their mechanisms of action remain poorly understood. Here, we characterize human SMC complexes condensin ... -
Hybrid Gene Origination Creates Human-Virus Chimeric Proteins during Infection.
(CELL PRESS, 2020-06-25)RNA viruses are a major human health threat. The life cycles of many highly pathogenic RNA viruses like influenza A virus (IAV) and Lassa virus depends on host mRNA, because viral polymerases cleave 5'-m7G-capped host ... -
Identification of autophagy-specific cargo and characterization of b-catenin as LC3/GABARAP interacting protein
(Institute of Cancer Research (University Of London), 2023-07-17)Autophagy is an evolutionary conserved eukaryotic degradation system induced under cellular stress conditions in which cellular components, such as damaged organelles, and aggregated proteins sequestrated through lysomal ... -
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 ... -
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 ...
