Results
- Showing results for:
- Reset all filters
Search results
-
Journal articleStanzione F, De Simone A, Esposito L, et al., 2012, , PROTEIN AND PEPTIDE LETTERS, Vol: 19, Pages: 846-851, ISSN: 0929-8665
- Cite
- Citations: 1
-
Journal articleKafasla P, Mickleburgh I, Llorian M, et al., 2012, , BIOCHEMICAL SOCIETY TRANSACTIONS, Vol: 40, Pages: 815-820, ISSN: 0300-5127
- Cite
- Citations: 74
-
Journal articleHarding CR, Schroeder GN, Reynolds S, et al., 2012, , INFECTION AND IMMUNITY, Vol: 80, Pages: 2780-2790, ISSN: 0019-9567
- Cite
- Citations: 88
-
Journal articleMontalvao RW, De Simone A, Vendruscolo M, 2012, , JOURNAL OF BIOMOLECULAR NMR, Vol: 53, Pages: 281-292, ISSN: 0925-2738
- Cite
- Citations: 46
-
Journal articleCarafoli F, Hussain S-A, Hohenester E, 2012, , PLOS ONE, Vol: 7, ISSN: 1932-6203
- Cite
- Citations: 47
-
Journal articleManka SW, Carafoli F, Visse R, et al., 2012, , PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Vol: 109, Pages: 12461-12466, ISSN: 0027-8424
- Cite
- Citations: 175
-
Journal articleKitney R, Freemont P, 2012, , FEBS LETTERS, Vol: 586, Pages: 2029-2036, ISSN: 0014-5793
- Cite
- Citations: 57
-
Journal articleLiu L-N, Bryan SJ, Huang F, et al., 2012, , PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Vol: 109, Pages: 11431-11436, ISSN: 0027-8424
- Cite
- Citations: 80
-
Journal articleMeredith TC, Wang H, Beaulieu P, et al., 2012, , Mob Genet Elements, Vol: 2, Pages: 171-178, ISSN: 2159-2543
Determining the mechanism of action of bacterial growth inhibitors can be a formidable challenge in the progression of small molecules into antibacterial therapies. To help address this bottleneck, we have developed a robust transposon mutagenesis system using a suite of outward facing promoters in order to generate a comprehensive range of expression genotypes in Staphylococcus aureus from which to select defined compound-resistant transposon insertion mutants. Resistance stemming from either gene or operon over/under-expression, in addition to deletion, provides insight into multiple factors that contribute to a compound's observed activity, including means of cell envelope penetration and susceptibility to efflux. By profiling the entire resistome, the suitability of an antibacterial target itself is also evaluated, sometimes with unanticipated results. We herein show that for the staphylococcal signal peptidase (SpsB) inhibitors, modulating expression of lipoteichoic acid synthase (LtaS) confers up to a 100-fold increase in the minimal inhibitory concentration. As similarly efficient transposition systems are or will become established in other bacteria and cell types, we discuss the utility, limitations and future promise of Tnp mutagenesis for determining both a compound's mechanism of action and in the evaluation of novel targets.
-
Journal articleWong ARC, Raymond B, Collins JW, et al., 2012, , CELLULAR MICROBIOLOGY, Vol: 14, Pages: 1051-1070, ISSN: 1462-5814
- Cite
- Citations: 29
-
Journal articleHare S, Maertens GN, Cherepanov P, 2012, , The EMBO Journal, Vol: 31, Pages: 3020-3028, ISSN: 0261-4189
Retroviral integrase (IN) is responsible for two consecutive reactions, which lead to insertion of a viral DNA copy into a host cell chromosome. Initially, the enzyme removes di or trinucleotides from viral DNA ends to expose 3′hydroxyls attached to the invariant CA dinucleotides (3′processing reaction). Second, it inserts the processed 3′viral DNA ends into host chromosomal DNA (strand transfer). Herein, we report a crystal structure of prototype foamy virus IN bound to viral DNA prior to 3′processing. Furthermore, taking advantage of its dependence on divalent metal ion cofactors, we were able to freeze trap the viral enzyme in its ground states containing all the components necessary for 3′processing or strand transfer. Our results shed light on the mechanics of retroviral DNA integration and explain why HIV IN strand transfer inhibitors are ineffective against the 3′processing step of integration. The ground state structures moreover highlight a striking substrate mimicry utilized by the inhibitors in their binding to the IN active site and suggest ways to improve upon this clinically relevant class of small molecules.
-
Journal articleDart AE, Donnelly SK, Holden DW, et al., 2012, , JOURNAL OF CELL SCIENCE, Vol: 125, Pages: 2825-2830, ISSN: 0021-9533
- Cite
- Citations: 35
-
Journal articleLeen EN, Baeza G, Curry S, 2012, , PLOS ONE, Vol: 7, ISSN: 1932-6203
- Cite
- Citations: 20
-
Journal articleMoyes DL, Murciano C, Tang S, et al., 2012,
Epithelial responses to <i>Candida albicans</i>
, MYCOSES, Vol: 55, Pages: 2-3, ISSN: 0933-7407 -
Journal articleMesquita FS, Thomas M, Sachse M, et al., 2012, , PLOS PATHOGENS, Vol: 8, ISSN: 1553-7366
- Cite
- Citations: 141
-
Journal articleKomenda J, Sobotka R, Nixon PJ, 2012, , CURRENT OPINION IN PLANT BIOLOGY, Vol: 15, Pages: 245-251, ISSN: 1369-5266
- Cite
- Citations: 219
-
Journal articleKato M, Cardona T, Rutherford AW, et al., 2012, , JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, Vol: 134, Pages: 8332-8335, ISSN: 0002-7863
- Cite
- Citations: 176
-
Journal articleLiu B, Garnett JA, Lee W-C, et al., 2012, , BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, Vol: 421, Pages: 208-213, ISSN: 0006-291X
- Cite
- Citations: 4
-
Journal articleVydyanath A, Gurnett CA, Marston S, et al., 2012, , Journal of Muscle Research and Cell Motility, Vol: 33, Pages: 61-74, ISSN: 1573-2657
Myosin binding protein-C (MyBP-C), a majorthick filament associated sarcomeric protein, plays animportant functional and structural role in regulating sarcomereassembly and crossbridge formation. Missing oraberrant MyBP-C proteins (both cardiac and skeletal) havebeen shown to cause both cardiac and skeletal myopathies,thereby emphasising its importance for the normal functioningof the sarcomere. Mutations in cardiac MyBP-C area major cause of hypertrophic cardiomyopathy (HCM),while mutations in skeletal MyBP-C have been implicatedin a disease of skeletal muscle—distal arthrogryposis type1 (DA-1). Here we report the first detailed electronmicroscopy studies on human cardiac and skeletal tissuescarrying MyBP-C gene mutations, using samples obtainedfrom HCM and DA-1 patients. We have used establishedimage averaging methods to identify and study the axialdistribution of MyBP-C on the thick filament by averagingprofile plots of the A-band of the sarcomere from electronmicrographs of human cardiac and skeletal myopathyspecimens. Due to the difficulty of obtaining normal humantissue, we compared the distribution to the A-band structurein normal frog skeletal, rat cardiac muscle and incardiac muscle of MyBP-C-deficient mice. Very similaroverall profile averages were obtained from the C-zones incardiac HCM samples and skeletal DA-1 samples withMyBP-C gene mutations, suggesting that mutations inMyBP-C do not
-
Journal articleFigueira R, Holden DW, 2012, , MICROBIOLOGY-SGM, Vol: 158, Pages: 1147-1161, ISSN: 1350-0872
- Cite
- Citations: 277
-
Journal articleDouzi B, Filloux A, Voulhoux R, 2012, , PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES, Vol: 367, Pages: 1059-1072, ISSN: 0962-8436
- Cite
- Citations: 97
-
Journal articleKuehrova P, De Simone A, Otyepka M, et al., 2012, , BIOPHYSICAL JOURNAL, Vol: 102, Pages: 1897-1906, ISSN: 0006-3495
- Cite
- Citations: 73
-
Journal articleCarafoli F, Mayer MC, Shiraishi K, et al., 2012, , STRUCTURE, Vol: 20, Pages: 688-697, ISSN: 0969-2126
- Cite
- Citations: 74
-
Journal articleSimpson PJ, Cota E, Bolanos-Garcia VM, 2012, , BIOMOLECULAR NMR ASSIGNMENTS, Vol: 6, Pages: 115-118, ISSN: 1874-2718
- Cite
- Citations: 1
-
Journal articleShah UV, Allenby MC, Williams DR, et al., 2012, , CRYSTAL GROWTH & DESIGN, Vol: 12, Pages: 1772-1777, ISSN: 1528-7483
- Cite
- Citations: 34
-
Journal articleEngelman A, Cherepanov P, 2012, , NATURE REVIEWS MICROBIOLOGY, Vol: 10, Pages: 279-290, ISSN: 1740-1526
- Cite
- Citations: 272
-
Journal articleFillet S, Daniels C, Pini C, et al., 2012, , ENVIRONMENTAL MICROBIOLOGY REPORTS, Vol: 4, Pages: 158-167, ISSN: 1758-2229
- Cite
- Citations: 17
-
Conference paperZhao XZ, Maddali K, Smith SJ, et al., 2012,
6,7-Dihydroxy-1-oxoisoindoline-4-sulfonamide-containing HIV-1 integrase inhibitors
, 243rd National Spring Meeting of the American-Chemical-Society, Publisher: AMER CHEMICAL SOC, ISSN: 0065-7727 -
Journal articleCamilloni C, De Simone A, Vranken WF, et al., 2012, , BIOCHEMISTRY, Vol: 51, Pages: 2224-2231, ISSN: 0006-2960
- Cite
- Citations: 298
-
Journal articleRutherford AW, Osyczka A, Rappaport F, 2012, , FEBS Lett, Vol: 586, Pages: 603-616
The energy-converting redox enzymes perform productive reactions efficiently despite the involvement of high energy intermediates in their catalytic cycles. This is achieved by kinetic control: with forward reactions being faster than competing, energy-wasteful reactions. This requires appropriate cofactor spacing, driving forces and reorganizational energies. These features evolved in ancestral enzymes in a low O(2) environment. When O(2) appeared, energy-converting enzymes had to deal with its troublesome chemistry. Various protective mechanisms duly evolved that are not directly related to the enzymes' principal redox roles. These protective mechanisms involve fine-tuning of reduction potentials, switching of pathways and the use of short circuits, back-reactions and side-paths, all of which compromise efficiency. This energetic loss is worth it since it minimises damage from reactive derivatives of O(2) and thus gives the organism a better chance of survival. We examine photosynthetic reaction centres, bc(1) and b(6)f complexes from this view point. In particular, the evolution of the heterodimeric PSI from its homodimeric ancestors is explained as providing a protective back-reaction pathway. This "sacrifice-of-efficiency-for-protection" concept should be generally applicable to bioenergetic enzymes in aerobic environments.
This data is extracted from the Web of Science and reproduced under a licence from Thomson Reuters. You may not copy or re-distribute this data in whole or in part without the written consent of the Science business of Thomson Reuters.