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Showing papers in "Journal of Molecular Biology in 2019"


Journal ArticleDOI
TL;DR: It is contended that issues including continuing unresolved questions around mechanism; opportunities afforded by new technologies such as serial femtosecond crystallography; the need for new inhibitors, particularly for MBLs; the likely impact of new β-lactam:inhibitor combinations and the continuing clinical importance of β- lactams mean that this remains a rewarding research area.

423 citations


Journal ArticleDOI
TL;DR: This work assesses whether a missense variant is structurally damaging by using experimental and predicted structures and shows that 40% of the 1965 disease-associated missense variants analyzed have aStructurally damaging change in the mutant structure.

284 citations


Journal ArticleDOI
TL;DR: How metals affect brain physiology and immunity, as well as their roles in the accumulation of toxic AD proteinaceous species (i.e., β-amyloid and tau) are reviewed to increase the awareness of metals as players in the onset and progression of AD.

240 citations


Journal ArticleDOI
TL;DR: An overview of the main physicochemical features that can be engineered to achieve enhanced bioactivity of antimicrobials is provided and current strategies being used to design AMPs are described.

229 citations


Journal ArticleDOI
TL;DR: This review summarizes current applications of the dCas tools for transcription regulation, epigenetic engineering, genome imaging, genetic screens, and chromatin immunoprecipitation and highlights the advantages and existing challenges.

217 citations


Journal ArticleDOI
TL;DR: This review will compare and contrast what is known about the molecular architecture and behavior of Type VI (A-D) CRISPR-Cas13 interference complexes, how this allows them to carry out their RNA-targeting function, how Type VI accessory proteins are able to modulate Cas13 activity, and how together all of these features have led to the rapid development of a range of RNA- targeting applications.

201 citations


Journal ArticleDOI
TL;DR: In this review, changes in biofilm physical structure during the transition from oral health to disease and the concomitant relationship between structure and community function will be emphasized.

147 citations


Journal ArticleDOI
TL;DR: It is likely only by combining the above approaches will the field fully elucidate the molecular pathways that regulate microglia and influence neurodegeneration, in turn uncovering potential new targets for future therapeutic development.

125 citations


Journal ArticleDOI
TL;DR: It is held that moral decision making should evolve as the science of genomic engineering advances and it would be reasonable for national and supranational legislatures to consider evidence-based regulation of certain CRISPR applications for the betterment of human health and progress.

106 citations


Journal ArticleDOI
TL;DR: Bacterial transcription termination occurs in three recognized ways: intrinsic termination, an activity only of the core RNAP enzyme and transcript sequences that encode an RNA hairpin and terminal uridine-rich segment; termination by the enzyme Rho, an ATP-dependent RNA translocase that releases RNA by forcing uncharacterized structural changes in the elongating complex.

96 citations


Journal ArticleDOI
TL;DR: It is argued that recombinant mimics of the envelope spike are currently capable of capturing many features of the native viral glycan shield, and strategies through which the immunogenicity of Env glycans may be enhanced in the development of future immunogens are explored.

Journal ArticleDOI
TL;DR: The main molecular players involved in promoting survival of senescent cells, with particular emphasis on the regulation of senescence-associated anti-apoptotic pathways are described and the consequences these pathways have in providing resistance to intrinsic and extrinsic pro-APoptotic signals are discussed.

Journal ArticleDOI
TL;DR: The complexity of ISG15 is reviewed within the context of viral infection, focusing primarily on its antiviral function and the mechanisms viruses employ to thwart its effects.

Journal ArticleDOI
TL;DR: Interestingly, fibril helical twists increased upon the removal of C-terminal residues and can be propagated through cross-seeding as well as increased electron densities in the N-terminus of Ac1-103, whereas the C- terminus ofAc1-122 appeared more structured.

Journal ArticleDOI
TL;DR: The data suggest that there are a number of previously unidentified ARE ABCFs in antibiotic producers and important human pathogens, and 45 distinct subfamilies of ABCFs that are widespread across bacterial and eukaryotic phyla are found.

Journal ArticleDOI
TL;DR: A new and highly versatile computational tool, the Channel Annotation Package (CHAP) that implements the methodology of molecular dynamics simulations of water as a proxy to predict hydrophobic gates, is presented.

Journal ArticleDOI
TL;DR: Evidence that link TA modules to antibiotic bacterial persistence is summarized and the limitations of work on these stress-responsive modules as well as bacterial persistence in general are discussed.

Journal ArticleDOI
TL;DR: This review describes the serendipitous discovery of INH, its effectiveness on TB patients, and early studies to discover its mechanisms of bacteriocidal activity, and portrays a detailed molecular analysis of INh killing and resistance mechanisms including persistence.

Journal ArticleDOI
TL;DR: Approaches that employ VR in scientific research based on some concrete examples are discussed and it is suggested that VR might soon merit the same level of attention to imaging data as machine learning currently has.

Journal ArticleDOI
TL;DR: An overview of the origins of antibiotic resistance is provided to highlight the crossroads of antibiotic biosynthesis and producer self-protection that result in clinically relevant resistance mechanisms.

Journal ArticleDOI
TL;DR: A new database is constructed to include genomic codon-pair and dinucleotide statistics of all organisms with sequenced genome, available in the GenBank, and is believed to be an invaluable tool to many researchers in academia and pharmaceutical industry.

Journal ArticleDOI
TL;DR: This review summarizes the GBS and host factors involved in GBS's state as both an asymptomatic colonizer and an invasive pathogen and identifies novel strategies to mitigate GBS virulence.

Journal ArticleDOI
TL;DR: Considering that many brain disorders are accompanied by changes in brain energy metabolism and sustained inflammation, and that energy metabolism has a strong influence on the inflammatory responses ofmicroglia, the emerging significance of microglial energy metabolism in neurodegeneration is highlighted in this review.

Journal ArticleDOI
TL;DR: Analysis of urine and bladder biopsy samples from postmenopausal women undergoing cystoscopy with fulguration of trigonitis in the advanced management of antibiotic-refractory RUTI provides conclusive evidence that bacteria invade the human urothelium and suggests that diverse bacterial species and the adaptive immune response play important roles in RUTi in humans.

Journal ArticleDOI
TL;DR: The interplay between the primary function of CRISPR-Cas as an adaptive immunity mechanism and these other roles defines the richness of the biological effects of these systems and affects their spread among bacteria and archaea.

Journal ArticleDOI
TL;DR: Understanding evolution in clonal biofilm populations will facilitate future studies in complex multispecies biofilms that are more representative of nature, and fast-evolving mobile genetic elements can unpredictably shift intra-species interactions in B. subtilisBiofilms.

Journal ArticleDOI
TL;DR: A simplified model for the catalytic cycle in which capture of the transported DNA segment causes conformational changes in the ATPase domain that push the DNA gate open, resulting in stretching and cleaving the gate-DNA in two steps is presented.

Journal ArticleDOI
TL;DR: Overall, the results evoke a central role for muscle autophagy in cancer-induced muscle wasting, and TP53INP2 further promoted atrogene expression and suppressed mitochondrial dynamics-related genes.

Journal ArticleDOI
TL;DR: A new EvoDesign server is proposed, which extends the principles of evolution-based design to design protein-protein interactions and should become a useful online tool for functional protein design and drug discovery studies.

Journal ArticleDOI
TL;DR: Current challenges limiting the utility of CRISPR-Cas screening as well as future research needed to resolve these impediments are described.