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complexNMR SIGNED

Structural Dynamics of Protein Complexes by Solid-State NMR

Total Cost €

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EC-Contrib. €

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Partnership

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 complexNMR project word cloud

Explore the words cloud of the complexNMR project. It provides you a very rough idea of what is the project "complexNMR" about.

unknown    lines    emerges    pkss    domains    truly    parts    engineering    worthless    solution    insights    solving    antibiotics    assembly    successful    harnessed    easily    threatening    modular    infections    holistic    tackled    enacyloxin    understand    puzzle    enzymatic    guide    bacteria    synthesize    life    interactions    sensitivity    solid    building    proteins    quantities    difficult    programmable    molecular    innovations    baumannii    natural    structural    probe    nanomole    complexes    biology    modeling    nmr    multidrug    resolution    missing    atomic    biosynthesis    dynamics    multicomponent    resistant    tuberculosis    time    chemically    function    motions    acquired    industry    global    turning    lab    multidisciplinary    measuring    acinetobacter    rooted    rational    drugs    synthetic    grave    synthases    render    polyketide    first    interacting    protein    hospital    mechanisms    arsenal    gladiolin    gigantic    structure    until    antibody   

Project "complexNMR" data sheet

The following table provides information about the project.

Coordinator
THE UNIVERSITY OF WARWICK 

Organization address
address: Kirby Corner Road - University House
city: COVENTRY
postcode: CV4 8UW
website: www.warwick.ac.uk

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country United Kingdom [UK]
 Project website https://warwick.ac.uk/fac/sci/chemistry/research/lewandowski/lewandowskigroup/
 Total cost 1˙999˙044 €
 EC max contribution 1˙999˙044 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2014-STG
 Funding Scheme ERC-STG
 Starting year 2015
 Duration (year-month-day) from 2015-05-01   to  2020-04-30

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    THE UNIVERSITY OF WARWICK UK (COVENTRY) coordinator 1˙999˙044.00

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 Project objective

Multidrug resistant bacteria that render worthless the current arsenal of antibiotics are a growing global problem. This grave challenge could be tackled by polyketide synthases (PKSs), which are gigantic modular enzymatic assembly lines for natural products. PKSs could be developed for industry to produce chemically difficult to synthesize drugs, but cannot be harnessed until we understand how they work on the molecular level. However, such understanding is missing because we cannot easily investigate large complexes with current structural biology and modeling methods. A key puzzle is how the function of these multicomponent systems emerges from atomic-scale interactions of their parts. Solving this puzzle requires a holistic approach involving measuring and modeling the relevant interacting parts together. Our goal is to develop a multidisciplinary approach rooted in solid and solution state NMR that will make possible studies of complexes from PKSs. The two main challenges for the NMR of PKSs are increasing sensitivity and resolution. Recent innovations from our lab allow application of solid-state to study large complexes in 2–10 nanomole quantities. Building on this approach, with a protein-antibody complex as a test case, we will develop new NMR methods that will enable a study of structure and motions of domains in complexes. We will probe, for the first time, the structural dynamics of PKSs of enacyloxin and gladiolin, which are antibiotics against life-threatening multidrug resistant hospital-acquired Acinetobacter baumannii infections and tuberculosis. These studies will guide rational engineering of the PKSs to enable synthetic biology approaches to produce new antibiotics. If successful, this project will go beyond the state of the art by: enabling studies of unknown proteins in large complexes and providing unique insights into novel mechanisms for controlling biosynthesis in PKSs, turning them into truly programmable synthetic biology devices.

 Publications

year authors and title journal last update
List of publications.
2019 A. Gallo, W.T. Franks, J.R. Lewandowski
A suite of solid-state NMR experiments to utilize orphaned magnetization for assignment of proteins using parallel high and low gamma detection
published pages: 219-231, ISSN: 1090-7807, DOI: 10.1016/j.jmr.2019.07.006
Journal of Magnetic Resonance 305 2019-12-17
2019 Carl Öster, Simone Kosol, Józef R. Lewandowski
Quantifying Microsecond Exchange in Large Protein Complexes with Accelerated Relaxation Dispersion Experiments in the Solid State
published pages: 1-10, ISSN: 2045-2322, DOI: 10.1038/s41598-019-47507-8
Scientific Reports 9/1 2019-12-17
2018 Carl Öster, Grzegorz P. Walkowiak, Dallas E. Hughes, Amy L. Spoering, Aaron J. Peoples, Anita C. Catherwood, Julie A. Tod, Adrian J. Lloyd, Torsten Herrmann, Kim Lewis, Christopher G. Dowson, Józef R. Lewandowski
Structural studies suggest aggregation as one of the modes of action for teixobactin
published pages: 8850-8859, ISSN: 2041-6520, DOI: 10.1039/c8sc03655a
Chemical Science 9/47 2019-12-17
2019 Simone Kosol, Angelo Gallo, Daniel Griffiths, Timothy R. Valentic, Joleen Masschelein, Matthew Jenner, Emmanuel L. C. de los Santos, Lucio Manzi, Paulina K. Sydor, Dean Rea, Shanshan Zhou, Vilmos Fülöp, Neil J. Oldham, Shiou-Chuan Tsai, Gregory L. Challis, Józef R. Lewandowski
Structural basis for chain release from the enacyloxin polyketide synthase
published pages: 913-923, ISSN: 1755-4330, DOI: 10.1038/s41557-019-0335-5
Nature Chemistry 11/10 2019-11-07
2017 Carl Öster, Simone Kosol, Christoph Hartlmüller, Jonathan M. Lamley, Dinu Iuga, Andres Oss, Mai-Liis Org, Kalju Vanatalu, Ago Samoson, Tobias Madl, Józef R. Lewandowski
Characterization of Protein–Protein Interfaces in Large Complexes by Solid-State NMR Solvent Paramagnetic Relaxation Enhancements
published pages: 12165-12174, ISSN: 0002-7863, DOI: 10.1021/jacs.7b03875
Journal of the American Chemical Society 139/35 2019-05-29
2018 Ulrich Sternberg, Raiker Witter, Ilya Kuprov, Jonathan M. Lamley, Andres Oss, Józef R. Lewandowski, Ago Samoson
1 H line width dependence on MAS speed in solid state NMR – Comparison of experiment and simulation
published pages: 32-39, ISSN: 1090-7807, DOI: 10.1016/j.jmr.2018.04.003
Journal of Magnetic Resonance 291 2019-05-29
2018 Matthew Jenner, Simone Kosol, Daniel Griffiths, Panward Prasongpholchai, Lucio Manzi, Andrew S Barrow, John E Moses, Neil J Oldham, Józef R Lewandowski, Gregory L Challis
Mechanism of intersubunit ketosynthase–dehydratase interaction in polyketide synthases
published pages: 270-275, ISSN: 1552-4450, DOI: 10.1038/nchembio.2549
Nature Chemical Biology 14/3 2019-05-29
2017 Daryl Good, Charlie Pham, Jacob Jagas, Józef R. Lewandowski, Vladimir Ladizhansky
Solid-State NMR Provides Evidence for Small-Amplitude Slow Domain Motions in a Multispanning Transmembrane α-Helical Protein
published pages: 9246-9258, ISSN: 0002-7863, DOI: 10.1021/jacs.7b03974
Journal of the American Chemical Society 139/27 2019-05-29
2015 Jonathan M. Lamley, Carl Öster, Rebecca A. Stevens, Józef R. Lewandowski
Intermolecular Interactions and Protein Dynamics by Solid-State NMR Spectroscopy
published pages: 15374-15378, ISSN: 1433-7851, DOI: 10.1002/anie.201509168
Angewandte Chemie International Edition 54/51 2019-05-24

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