52 Result(s)

Article

Mutational spectra are associated with bacterial niche

As observed in cancers, individual mutagens and defects in DNA repair create distinctive mutational signatures that combine to form context-specific spectra within cells. We reasoned that similar processes mus...

Christopher Ruis, Aaron Weimann, Gerry Tonkin-Hill… in Nature Communications (2023)

Article

Human DNA-dependent protein kinase activation mechanism

DNA-dependent protein kinase (DNA-PK), a multicomponent complex including the DNA-PK catalytic subunit and Ku70/80 heterodimer together with DNA, is central to human DNA damage response and repair. Using a DNA...

Shikang Liang, Tom L. Blundell in Nature Structural & Molecular Biology (2023)

Article

Mycobacterium abscessus pathogenesis identified by phenogenomic analyses

The medical and scientific response to emerging and established pathogens is often severely hampered by ignorance of the genetic determinants of virulence, drug resistance and clinical outcomes that could be u...

Lucas Boeck, Sophie Burbaud, Marcin Skwark, Will H. Pearson… in Nature Microbiology (2022)

Article

Structural insights into inhibitor regulation of the DNA repair protein DNA-PKcs

The DNA-dependent protein kinase catalytic subunit (DNA-PKcs) has a central role in non-homologous end joining, one of the two main pathways that detect and repair DNA double-strand breaks (DSBs) in humans^1,2. DN...

Shikang Liang, Sherine E. Thomas, Amanda K. Chaplin, Steven W. Hardwick… in Nature (2022)

Article

A base measure of precision for protein stability predictors: structural sensitivity

Prediction of the change in fold stability (ΔΔG) of a protein upon mutation is of major importance to protein engineering and screening of disease-causing variants. Many prediction methods can use 3D structura...

Octav Caldararu, Tom L. Blundell, Kasper P. Kepp in BMC Bioinformatics (2021)

Article

Inhibiting Mycobacterium tuberculosis CoaBC by targeting an allosteric site

Coenzyme A (CoA) is a fundamental co-factor for all life, involved in numerous metabolic pathways and cellular processes, and its biosynthetic pathway has raised substantial interest as a drug target against m...

Vitor Mendes, Simon R. Green, Joanna C. Evans, Jeannine Hess… in Nature Communications (2021)

Article

Identification and Characterization of Genetic Determinants of Isoniazid and Rifampicin Resistance in Mycobacterium tuberculosis in Southern India

Drug-resistant tuberculosis (TB), one of the leading causes of death worldwide, arises mainly from spontaneous mutations in the genome of Mycobacterium tuberculosis. There is an urgent need to understand the mech...

Asma Munir, Narender Kumar, Suresh Babu Ramalingam… in Scientific Reports (2019)

Article

The deubiquitylating enzyme UCHL3 regulates Ku80 retention at sites of DNA damage

Non-homologous end-joining (NHEJ), which can promote genomic instability when dysfunctional, is a major DNA double-strand break (DSB) repair pathway. Although ubiquitylation of the core NHEJ factor, Ku (Ku70-K...

Ryotaro Nishi, Paul W. G. Wijnhoven, Yusuke Kimura, Misaki Matsui… in Scientific Reports (2018)

Article

Publisher Correction: Structural Implications of Mutations Conferring Rifampin Resistance in Mycobacterium leprae

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.

Sundeep Chaitanya Vedithi, Sony Malhotra, Madhusmita Das… in Scientific Reports (2018)

Article

Structural Implications of Mutations Conferring Rifampin Resistance in Mycobacterium leprae

The rpoB gene encodes the β subunit of RNA polymerase holoenzyme in Mycobacterium leprae (M. leprae). Missense mutations in the rpoB gene were identified as etiological factors for rifampin resistance in leprosy....

Sundeep Chaitanya Vedithi, Sony Malhotra, Madhusmita Das… in Scientific Reports (2018)

Article

mCSM-lig: quantifying the effects of mutations on protein-small molecule affinity in genetic disease and emergence of drug resistance

The ability to predict how a mutation affects ligand binding is an essential step in understanding, anticipating and improving the design of new treatments for drug resistance and in understanding genetic dise...

Douglas E. V. Pires, Tom L. Blundell, David B. Ascher in Scientific Reports (2016)

Article

In silico functional dissection of saturation mutagenesis: Interpreting the relationship between phenotypes and changes in protein stability, interactions and activity

Despite interest in associating polymorphisms with clinical or experimental phenotypes, functional interpretation of mutation data has lagged behind generation of data from modern high-throughput techniques an...

Douglas E. V. Pires, **g Chen, Tom L. Blundell, David B. Ascher in Scientific Reports (2016)

Article

Structure of Mycobacterium thermoresistibile GlgE defines novel conformational states that contribute to the catalytic mechanism

GlgE, an enzyme of the pathway that converts trehalose to α-glucans, is essential for Mycobacterium tuberculosis. Inhibition of GlgE, which transfers maltose from a maltose-1-phosphate donor to α-glucan/maltoolig...

Vitor Mendes, Michal Blaszczyk, Ana Maranha, Nuno Empadinhas… in Scientific Reports (2015)

Article

Polyphony: superposition independent methods for ensemble-based drug discovery

Structure-based drug design is an iterative process, following cycles of structural biology, computer-aided design, synthetic chemistry and bioassay. In favorable circumstances, this process can lead to the st...

William R Pitt, Rinaldo W Montalvão, Tom L Blundell in BMC Bioinformatics (2014)

Article

The crystal structure of fibroblast growth factor 18 (FGF18)

Alan Brown, Lucy E. Adam, Tom L. Blundell in Protein & Cell (2014)

Article

Comprehensive, atomic-level characterization of structurally characterized protein-protein interactions: the PICCOLO database

Structural studies are increasingly providing huge amounts of information on multi-protein assemblies. Although a complete understanding of cellular processes will be dependent on an explicit characterization ...

George R Bickerton, Alicia P Higueruelo, Tom L Blundell in BMC Bioinformatics (2011)