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Journal articleStanzione F, De Simone A, Esposito L, et al., 2012,
Dynamical Properties of Steric Zipper Polymorphs Formed by a IAPP-Derived Peptide
, PROTEIN AND PEPTIDE LETTERS, Vol: 19, Pages: 846-851, ISSN: 0929-8665- Author Web Link
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- Citations: 1
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Journal articleMontalvao RW, De Simone A, Vendruscolo M, 2012,
Determination of structural fluctuations of proteins from structure-based calculations of residual dipolar couplings
, JOURNAL OF BIOMOLECULAR NMR, Vol: 53, Pages: 281-292, ISSN: 0925-2738- Author Web Link
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- Citations: 47
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Journal articleKafasla P, Mickleburgh I, Llorian M, et al., 2012,
Defining the roles and interactions of PTB
, BIOCHEMICAL SOCIETY TRANSACTIONS, Vol: 40, Pages: 815-820, ISSN: 0300-5127- Author Web Link
- Open Access Link
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- Citations: 61
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Journal articleManka SW, Carafoli F, Visse R, et al., 2012,
Structural insights into triple-helical collagen cleavage by matrix metalloproteinase 1
, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Vol: 109, Pages: 12461-12466, ISSN: 0027-8424- Author Web Link
- Open Access Link
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- Citations: 152
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Journal articleCarafoli F, Hussain S-A, Hohenester E, 2012,
Crystal Structures of the Network-Forming Short-Arm Tips of the Laminin β1 and γ1 Chains
, PLOS ONE, Vol: 7, ISSN: 1932-6203- Author Web Link
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- Citations: 41
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Journal articleKitney R, Freemont P, 2012,
Synthetic biology - the state of play
, FEBS LETTERS, Vol: 586, Pages: 2029-2036, ISSN: 0014-5793- Author Web Link
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- Citations: 51
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Journal articleLiu L-N, Bryan SJ, Huang F, et al., 2012,
Control of electron transport routes through redox-regulated redistribution of respiratory complexes
, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Vol: 109, Pages: 11431-11436, ISSN: 0027-8424- Author Web Link
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- Citations: 71
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Journal articleMeredith TC, Wang H, Beaulieu P, et al., 2012,
Harnessing the power of transposon mutagenesis for antibacterial target identification and evaluation.
, Mob Genet Elements, Vol: 2, Pages: 171-178, ISSN: 2159-2543Determining 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.
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Journal articleWong ARC, Raymond B, Collins JW, et al., 2012,
The enteropathogenic E. coli effector EspH promotes actin pedestal formation and elongation via WASP-interacting protein (WIP)
, CELLULAR MICROBIOLOGY, Vol: 14, Pages: 1051-1070, ISSN: 1462-5814- Author Web Link
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- Citations: 24
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Journal articleHare S, Maertens GN, Cherepanov P, 2012,
3 '-Processing and strand transfer catalysed by retroviral integrase in crystallo
, The EMBO Journal, Vol: 31, Pages: 3020-3028, ISSN: 0261-4189Retroviral 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.
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Journal articleDart AE, Donnelly SK, Holden DW, et al., 2012,
Nck and Cdc42 co-operate to recruit N-WASP to promote FcγR-mediated phagocytosis
, JOURNAL OF CELL SCIENCE, Vol: 125, Pages: 2825-2830, ISSN: 0021-9533- Author Web Link
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- Citations: 31
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Journal articleLeen EN, Baeza G, Curry S, 2012,
Structure of a Murine Norovirus NS6 Protease-Product Complex Revealed by Adventitious Crystallisation
, PLOS ONE, Vol: 7, ISSN: 1932-6203- Author Web Link
- Open Access Link
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- Citations: 20
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Journal articleMesquita FS, Thomas M, Sachse M, et al., 2012,
The <i>Salmonella</i> Deubiquitinase SseL Inhibits Selective Autophagy of Cytosolic Aggregates
, PLOS PATHOGENS, Vol: 8, ISSN: 1553-7366- Author Web Link
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- Citations: 121
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Journal articleKomenda J, Sobotka R, Nixon PJ, 2012,
Assembling and maintaining the Photosystem II complex in chloroplasts and cyanobacteria
, CURRENT OPINION IN PLANT BIOLOGY, Vol: 15, Pages: 245-251, ISSN: 1369-5266- Author Web Link
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- Citations: 201
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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 articleKato M, Cardona T, Rutherford AW, et al., 2012,
Photoelectrochemical Water Oxidation with Photosystem II Integrated in a Mesoporous; Indium Tin Oxide Electrode
, JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, Vol: 134, Pages: 8332-8335, ISSN: 0002-7863- Author Web Link
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- Citations: 165
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Journal articleLiu B, Garnett JA, Lee W-C, et al., 2012,
Promoting crystallisation of the <i>Salmonella enteritidis</i> fimbriae 14 pilin SefD using deuterium oxide
, BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, Vol: 421, Pages: 208-213, ISSN: 0006-291X- Author Web Link
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- Citations: 3
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Journal articleVydyanath A, Gurnett CA, Marston S, et al., 2012,
Axial distribution of myosin binding protein-C is unaffected by mutations in human cardiac and skeletal muscle
, Journal of Muscle Research and Cell Motility, Vol: 33, Pages: 61-74, ISSN: 1573-2657Myosin 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
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Journal articleFigueira R, Holden DW, 2012,
Functions of the <i>Salmonella</i> pathogenicity island 2 (SPI-2) type III secretion system effectors
, MICROBIOLOGY-SGM, Vol: 158, Pages: 1147-1161, ISSN: 1350-0872- Author Web Link
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- Citations: 246
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Journal articleDouzi B, Filloux A, Voulhoux R, 2012,
On the path to uncover the bacterial type II secretion system
, PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES, Vol: 367, Pages: 1059-1072, ISSN: 0962-8436- Author Web Link
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- Citations: 89
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Journal articleKuehrova P, De Simone A, Otyepka M, et al., 2012,
Force-Field Dependence of Chignolin Folding and Misfolding: Comparison with Experiment and Redesign
, BIOPHYSICAL JOURNAL, Vol: 102, Pages: 1897-1906, ISSN: 0006-3495- Author Web Link
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- Citations: 64
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Journal articleCarafoli F, Mayer MC, Shiraishi K, et al., 2012,
Structure of the Discoidin Domain Receptor 1 Extracellular Region Bound to an Inhibitory Fab Fragment Reveals Features Important for Signaling
, STRUCTURE, Vol: 20, Pages: 688-697, ISSN: 0969-2126- Author Web Link
- Open Access Link
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- Citations: 66
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Journal articleFillet S, Daniels C, Pini C, et al., 2012,
Transcriptional control of the main aromatic hydrocarbon efflux pump in <i>Pseudomonas</i>
, ENVIRONMENTAL MICROBIOLOGY REPORTS, Vol: 4, Pages: 158-167, ISSN: 1758-2229- Author Web Link
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- Citations: 17
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Journal articleSimpson PJ, Cota E, Bolanos-Garcia VM, 2012,
<SUP>1</SUP>H, <SUP>13</SUP>C and <SUP>15</SUP>N resonance assignments of the kinetochore localisation domain of BUBR1, a central component of the spindle assembly checkpoint
, BIOMOLECULAR NMR ASSIGNMENTS, Vol: 6, Pages: 115-118, ISSN: 1874-2718- Author Web Link
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- Citations: 1
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Journal articleShah UV, Allenby MC, Williams DR, et al., 2012,
Crystallization of Proteins at Ultralow Supersaturations Using Novel Three-Dimensional Nanotemplates
, CRYSTAL GROWTH & DESIGN, Vol: 12, Pages: 1772-1777, ISSN: 1528-7483- Author Web Link
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- Citations: 31
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Journal articleEngelman A, Cherepanov P, 2012,
The structural biology of HIV-1: mechanistic and therapeutic insights
, NATURE REVIEWS MICROBIOLOGY, Vol: 10, Pages: 279-290, ISSN: 1740-1526- Author Web Link
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- Citations: 225
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Journal articleCamilloni C, De Simone A, Vranken WF, et al., 2012,
Determination of Secondary Structure Populations in Disordered States of Proteins Using Nuclear Magnetic Resonance Chemical Shifts
, BIOCHEMISTRY, Vol: 51, Pages: 2224-2231, ISSN: 0006-2960- Author Web Link
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- Citations: 263
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Journal articleRutherford AW, Osyczka A, Rappaport F, 2012,
Back-reactions, short-circuits, leaks and other energy wasteful reactions in biological electron transfer: Redox tuning to survive life in O(2).
, FEBS Lett, Vol: 586, Pages: 603-616The 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.
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Journal articleNiwa H, Ewens CA, Tsang C, et al., 2012,
The Role of the N-Domain in the ATPase Activity of the Mammalian AAA ATPase p97/VCP
, JOURNAL OF BIOLOGICAL CHEMISTRY, Vol: 287, Pages: 8561-8570- Author Web Link
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- Citations: 90
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Journal articleCamilloni C, Robustelli P, De Simone A, et al., 2012,
Characterization of the Conformational Equilibrium between the Two Major Substates of RNase A Using NMR Chemical Shifts.
, J Am Chem Soc, Vol: 134, Pages: 3968-3971Following the recognition that NMR chemical shifts can be used for protein structure determination, rapid advances have recently been made in methods for extending this strategy for proteins and protein complexes of increasing size and complexity. A remaining major challenge is to develop approaches to exploit the information contained in the chemical shifts about conformational fluctuations in native states of proteins. In this work we show that it is possible to determine an ensemble of conformations representing the free energy surface of RNase A using chemical shifts as replica-averaged restraints in molecular dynamics simulations. Analysis of this surface indicates that chemical shifts can be used to characterize the conformational equilibrium between the two major substates of this protein.
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