20 Result(s)
within
Tom L Blundell
Science, Humanities and Social Sciences, multidisciplinary
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Article
Open AccessMutational 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...
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Open AccessStructural 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 humans1,2. DN...
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Article
Open AccessInhibiting 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...
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Article
Open AccessIdentification 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...
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Article
Open AccessThe 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...
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Article
Open AccessPublisher 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.
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Article
Open AccessStructural 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....
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Open AccessmCSM-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...
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Article
Open AccessIn 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...
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Article
Open AccessStructure 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...
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Article
Crystal structure of DNA-PKcs reveals a large open-ring cradle comprised of HEAT repeats
Several members of the phosphatidylinositol-3-OH kinase (PI(3)K) family are involved in the response to DNA double-strand breaks. One of these, DNA-dependent protein kinase (DNA-PK), is comprised of three subu...
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Article
Brief encounters bolster contacts
Molecules often work together in complexes to carry out their functions in the cell. But how do they get together in such a dynamic environment? A structural study follows proteins as they meet their partners.
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Article
Insights into DNA recombination from the structure of a RAD51–BRCA2 complex
The breast cancer susceptibility protein BRCA2 controls the function of RAD51, a recombinase enzyme, in pathways for DNA repair by homologous recombination. We report here the structure of a complex between an...
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Article
Crystal structure of fibroblast growth factor receptor ectodomain bound to ligand and heparin
Fibroblast growth factors (FGFs) are a large family of structurally related proteins with a wide range of physiological and pathological activities1. Signal transduction requires association of FGF with its recep...
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Article
Crystal structure of the complex of the cyclin D-dependent kinase Cdk6 bound to the cell-cycle inhibitor p19INK4d
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Article
Crystal structure of the complex of the cyclin D-dependent kinase Cdk6 bound to the cell-cycle inhibitor p19INK4d
The crystal structure of the cyclin D-dependent kinase Cdk6 bound to the p19INK4d protein has been determined at 1.9 Å resolution. The results provide the first structural information for a cyclin D-dependent pro...
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Article
Crystallographic data deposition
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Article
Structure of pentameric human serum amyloid P component
The three-dimensional structure of pentameric human serum amyloid P component at high resolution, the first reported for a pentraxin, reveals that the tertiary fold is remarkably similar to that of the legume ...
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Article
Structure of porphobilinogen deaminase reveals a flexible multidomain polymerase with a single catalytic site
The three-domain structure of porphobilinogen deaminase, a key enzyme in the biosynthetic pathway of tetrapyrroles, has been defined by X-ray analysis at 1.9 Å resolution. Two of the domains structurally resem...
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Article
New protein fold revealed by a 2.3-Å resolution crystal structure of nerve growth factor
NERVE growth factor (NGF)1is a member of an expanding family of neurotrophic factors (including brain-derived neurotrophic factor2 and the neurotrophins3,4) that control the development and survival of certain ne...
