Search Results

You searched for all publications:

with publication states 'Published (Approved)'

Search Again...

These results only include publications that have been reviewed and processed by Diamond Light Source. To also view papers that have not yet been processed click here.

You can use the folder icon under Actions to collate papers as required. You can then click on View Folder in the left-hand navigation to review and/or download your folder.

Exact matches
Related results

7 items found (0 items not approved), displaying all items.1

Instruments / Technical Area	Publication Details	Published
I21-Resonant Inelastic X-ray Scattering (RIXS)	Magnetic excitations in Nd𝑛+1Ni𝑛O3𝑛+1 Ruddlesden-Popper nickelates observed via resonant inelastic X-ray scattering Sophia F. R. Tenhuisen , Grace A. Pan , Qi Song , Denitsa R. Baykusheva , Dan Ferenc Segedin , Berit H. Goodge , Hanjong Paik , Jonathan Pelliciari , Valentina Bisogni , Yanhong Gu , Stefano Agrestini , Abhishek Nag , Mirian Garcia-Fernandez , Ke-Jin Zhou , Lena F. Kourkoutis , Charles M. Brooks , Julia E. A. Mundy , Mark P. M. Dean , Matteo Mitrano Physical Review B 111 DOI: 10.1103/PhysRevB.111.165145 Diamond Proposal Number(s): [27484] Show Abstract ▼ Abstract: Magnetic interactions are thought to play a key role in the properties of many unconventional superconductors, including cuprates, iron pnictides, and square-planar nickelates. Superconductivity was also recently observed in the bilayer and trilayer Ruddlesden-Popper nickelates, the electronic structure of which is expected to differ from that of cuprates and square-planar nickelates. Here we study how electronic structure and magnetic interactions evolve with the number of layers, 𝑛, in thin film Ruddlesden-Popper nickelates Nd𝑛+1⁢Ni𝑛⁢O3⁢𝑛+1 with 𝑛=1,3, and 5 using resonant inelastic x-ray scattering (RIXS). The RIXS spectra are consistent with a high-spin \|3⁢𝑑8⁢ 𝐿 ̲ ⟩ electronic configuration, resembling that of La2−𝑥⁢Sr𝑥⁢NiO4 and the parent perovskite, NdNiO3. The magnetic excitations soften to lower energy in the structurally self-doped, higher-𝑛 films. Our observations confirm that structural tuning is an effective route for altering electronic properties, such as magnetic superexchange, in this prominent family of materials.	Apr 2025
I03-Macromolecular Crystallography I04-1-Macromolecular Crystallography (fixed wavelength)	KorB switching from DNA-sliding clamp to repressor mediates long-range gene silencing in a multi-drug resistance plasmid Thomas C. Mclean , Francisco Balaguer-Pérez , Joshua Chandanani , Christopher M. Thomas , Clara Aicart-Ramos , Sophia Burick , Paul Dominic B. Olinares , Giulia Gobbato , Julia E. A. Mundy , Brian T. Chait , David M. Lawson , Seth A. Darst , Elizabeth A. Campbell , Fernando Moreno-Herrero , Tung Le Nature Microbiology 20 DOI: 10.1038/s41564-024-01915-3 Diamond Proposal Number(s): [25108] Open Access Show Abstract ▼ Abstract: Examples of long-range gene regulation in bacteria are rare and generally thought to involve DNA looping. Here, using a combination of biophysical approaches including X-ray crystallography and single-molecule analysis for the KorB–KorA system in Escherichia coli, we show that long-range gene silencing on the plasmid RK2, a source of multi-drug resistance across diverse Gram-negative bacteria, is achieved cooperatively by a DNA-sliding clamp, KorB, and a clamp-locking protein, KorA. We show that KorB is a CTPase clamp that can entrap and slide along DNA to reach distal target promoters up to 1.5 kb away. We resolved the tripartite crystal structure of a KorB–KorA–DNA co-complex, revealing that KorA latches KorB into a closed clamp state. DNA-bound KorA thus stimulates repression by stalling KorB sliding at target promoters to occlude RNA polymerase holoenzymes. Together, our findings explain the mechanistic basis for KorB role switching from a DNA-sliding clamp to a co-repressor and provide an alternative mechanism for long-range regulation of gene expression in bacteria.	Jan 2025
I04-Macromolecular Crystallography	Exploring the interaction of N-(benzothiazol-2-yl)pyrrolamide DNA gyrase inhibitors with the GyrB ATP-binding site lipophilic floor: A medicinal chemistry and QTAIM study Nace Zidar , Andrej Emanuel Cotman , Wessel Sinnige , Ondrej Benek , Michaela Barančokova , Anamarija Zega , Lucija Peterlin Mašič , Tihomir Tomašič , Janez Ilaš , Sara R. Henderson , Julia E. A. Mundy , Anthony Maxwell , Clare E. M. Stevenson , David M. Lawson , Geert Jan Sterk , Rodrigo Tosso , Lucas Gutierrez , Ricardo D. Enriz , Danijel Kikelj Bioorganic & Medicinal Chemistry 43 DOI: 10.1016/j.bmc.2024.117798 Diamond Proposal Number(s): [18565] Open Access Show Abstract ▼ Abstract: N-(Benzothiazole-2-yl)pyrrolamide DNA gyrase inhibitors with benzyl or phenethyl substituents attached to position 3 of the benzothiazole ring or to the carboxamide nitrogen atom were prepared and studied for their inhibition of Escherichia coli DNA gyrase by supercoiling assay. Compared to inhibitors bearing the substituents at position 4 of the benzothiazole ring, the inhibition was attenuated by moving the substituent to position 3 and further to the carboxamide nitrogen atom. A co-crystal structure of (Z)-3-benzyl-2-((4,5-dibromo-1H-pyrrole-2-carbonyl)imino)-2,3-dihydrobenzo[d]-thiazole-6-carboxylic acid (I) in complex with E. coli GyrB24 (ATPase subdomain) was solved, revealing the binding mode of this type of inhibitor to the ATP-binding pocket of the E. coli GyrB subunit. The key binding interactions were identified and their contribution to binding was rationalised by quantum theory of atoms in molecules (QTAIM) analysis. Our study shows that the benzyl or phenethyl substituents bound to the benzothiazole core interact with the lipophilic floor of the active site, which consists mainly of residues Gly101, Gly102, Lys103 and Ser108. Compounds with substituents at position 3 of the benzothiazole core were up to two orders of magnitude more effective than compounds with substituents at the carboxamide nitrogen. In addition, the 6-oxalylamino compounds were more potent inhibitors of E. coli DNA gyrase than the corresponding 6-acetamido analogues.	Jun 2024
I04-Macromolecular Crystallography	New dual inhibitors of bacterial topoisomerases with broad-spectrum antibacterial activity and in vivo efficacy against vancomycin-intermediate Staphylococcus aureus Martina Durcik , Andrej Emanuel Cotman , Žan Toplak , Štefan Možina , Žiga Skok , Petra Eva Szili , Márton Czikkely , Elvin Maharramov , Thu Hien Vu , Maria Vittoria Piras , Nace Zidar , Janez Ilaš , Anamarija Zega , Jurij Trontelj , Luis A. Pardo , Diarmaid Hughes , Douglas Huseby , Tália Berruga-Fernández , Sha Cao , Ivailo Simoff , Richard Svensson , Sergiy V. Korol , Zhe Jin , Francisca Vicente , Maria C. Ramos , Julia E. A. Mundy , Anthony Maxwell , Clare E. M. Stevenson , David M. Lawson , Björn Glinghammar , Eva Sjöström , Martin Bohlin , Joanna Oreskär , Sofie Alvér , Guido V. Janssen , Geert Jan Sterk , Danijel Kikelj , Csaba Pal , Tihomir Tomašič , Lucija Peterlin Mašič Journal Of Medicinal Chemistry 1703 DOI: 10.1021/acs.jmedchem.2c01905 Diamond Proposal Number(s): [25108] Open Access Show Abstract ▼ Abstract: A new series of dual low nanomolar benzothiazole inhibitors of bacterial DNA gyrase and topoisomerase IV were developed. The resulting compounds show excellent broad-spectrum antibacterial activities against Gram-positive Enterococcus faecalis, Enterococcus faecium and multidrug resistant (MDR) Staphylococcus aureus strains [best compound minimal inhibitory concentrations (MICs): range, <0.03125–0.25 μg/mL] and against the Gram-negatives Acinetobacter baumannii and Klebsiella pneumoniae (best compound MICs: range, 1–4 μg/mL). Lead compound 7a was identified with favorable solubility and plasma protein binding, good metabolic stability, selectivity for bacterial topoisomerases, and no toxicity issues. The crystal structure of 7a in complex with Pseudomonas aeruginosa GyrB24 revealed its binding mode at the ATP-binding site. Expanded profiling of 7a and 7h showed potent antibacterial activity against over 100 MDR and non-MDR strains of A. baumannii and several other Gram-positive and Gram-negative strains. Ultimately, in vivo efficacy of 7a in a mouse model of vancomycin-intermediate S. aureus thigh infection was also demonstrated.	Mar 2023
I03-Macromolecular Crystallography I04-1-Macromolecular Crystallography (fixed wavelength) I04-Macromolecular Crystallography I24-Microfocus Macromolecular Crystallography	Discovery and hit-to-lead optimization of benzothiazole scaffold-based DNA gyrase inhibitors with potent activity against Acinetobacter baumannii and Pseudomonas aeruginosa Andrej Emanuel Cotman , Martina Durcik , Davide Benedetto Tiz , Federica Fulgheri , Daniela Secci , Maša Sterle , Štefan Možina , Žiga Skok , Nace Zidar , Anamarija Zega , Janez Ilaš , Lucija Peterlin Mašič , Tihomir Tomašič , Diarmaid Hughes , Douglas L. Huseby , Sha Cao , Linnéa Garoff , Talía Berruga Fernández , Paraskevi Giachou , Lisa Crone , Ivailo Simoff , Richard Svensson , Bryndis Birnir , Sergiy V. Korol , Zhe Jin , Francisca Vicente , Maria C. Ramos , Mercedes De La Cruz , Björn Glinghammar , Lena Lenhammar , Sara R. Henderson , Julia E. A. Mundy , Anthony Maxwell , Claren E. M. Stevenson , David M. Lawson , Guido V. Janssen , Geert Jan Sterk , Danijel Kikelj Journal Of Medicinal Chemistry DOI: 10.1021/acs.jmedchem.2c01597 Diamond Proposal Number(s): [18565, 25108] Open Access Show Abstract ▼ Abstract: We have developed compounds with a promising activity against Acinetobacter baumannii and Pseudomonas aeruginosa, which are both on the WHO priority list of antibiotic-resistant bacteria. Starting from DNA gyrase inhibitor 1, we identified compound 27, featuring a 10-fold improved aqueous solubility, a 10-fold improved inhibition of topoisomerase IV from A. baumannii and P. aeruginosa, a 10-fold decreased inhibition of human topoisomerase IIα, and no cross-resistance to novobiocin. Cocrystal structures of 1 in complex with Escherichia coli GyrB24 and (S)-27 in complex with A. baumannii GyrB23 and P. aeruginosa GyrB24 revealed their binding to the ATP-binding pocket of the GyrB subunit. In further optimization steps, solubility, plasma free fraction, and other ADME properties of 27 were improved by fine-tuning of lipophilicity. In particular, analogs of 27 with retained anti-Gram-negative activity and improved plasma free fraction were identified. The series was found to be nongenotoxic, nonmutagenic, devoid of mitochondrial toxicity, and possessed no ion channel liabilities.	Jan 2023
I03-Macromolecular Crystallography I04-Macromolecular Crystallography	The pentapeptide-repeat protein, MfpA, interacts with mycobacterial DNA gyrase as a DNA T-segment mimic Lipeng Feng , Julia E. A. Mundy , Clare E. M. Stevenson , Lesley A. Mitchenall , David M. Lawson , Kaixia Mi , Anthony Maxwell Proceedings Of The National Academy Of Sciences 118 DOI: 10.1073/pnas.2016705118 Diamond Proposal Number(s): [1856] Open Access Show Abstract ▼ Abstract: DNA gyrase, a type II topoisomerase, introduces negative supercoils into DNA using ATP hydrolysis. The highly effective gyrase-targeted drugs, fluoroquinolones (FQs), interrupt gyrase by stabilizing a DNA-cleavage complex, a transient intermediate in the supercoiling cycle, leading to double-stranded DNA breaks. MfpA, a pentapeptide-repeat protein in mycobacteria, protects gyrase from FQs, but its molecular mechanism remains unknown. Here, we show that Mycobacterium smegmatis MfpA (MsMfpA) inhibits negative supercoiling by M. smegmatis gyrase (Msgyrase) in the absence of FQs, while in their presence, MsMfpA decreases FQ-induced DNA cleavage, protecting the enzyme from these drugs. MsMfpA stimulates the ATPase activity of Msgyrase by directly interacting with the ATPase domain (MsGyrB47), which was confirmed through X-ray crystallography of the MsMfpA–MsGyrB47 complex, and mutational analysis, demonstrating that MsMfpA mimics a T (transported) DNA segment. These data reveal the molecular mechanism whereby MfpA modulates the activity of gyrase and may provide a general molecular basis for the action of other pentapeptide-repeat proteins.	Mar 2021
I04-Macromolecular Crystallography	Exploring the chemical space of benzothiazole-based DNA gyrase B inhibitors Žiga Skok , Michaela Barančoková , Ondřej Benek , Cristina Durante Cruz , Päivi Tammela , Tihomir Tomašič , Nace Zidar , Lucija Peterlin Mašič , Anamarija Zega , Clare E. M. Stevenson , Julia E. A. Mundy , David M. Lawson , Anthony Maxwell , Danijel Kikelj , Janez Ilaš Acs Medicinal Chemistry Letters DOI: 10.1021/acsmedchemlett.0c00416 Diamond Proposal Number(s): [18565] Open Access Show Abstract ▼ Abstract: We designed and synthesized a series of inhibitors of the bacterial enzymes DNA gyrase and DNA topoisomerase IV, based on our recently published benzothiazole-based inhibitor bearing an oxalyl moiety. To improve the antibacterial activity and retain potent enzymatic activity, we systematically explored the chemical space. Several strategies of modification were followed: varying substituents on the pyrrole carboxamide moiety, alteration of the central scaffold, including variation of substitution position and, most importantly, modification of the oxalyl moiety. Compounds with acidic, basic, and neutral properties were synthesized. To understand the mechanism of action and binding mode, we have obtained a crystal structure of compound 16a, bearing a primary amino group, in complex with the N-terminal domain of E. coli gyrase B (24 kDa) (PDB: 6YD9). Compound 15a, with a low molecular weight of 383 Da, potent inhibitory activity on E. coli gyrase (IC50 = 9.5 nM), potent antibacterial activity on E. faecalis (MIC = 3.13 μM), and efflux impaired E. coli strain (MIC = 0.78 μM), is an important contribution for the development of novel gyrase and topoisomerase IV inhibitors in Gram-negative bacteria.	Oct 2020

Publications Database

Search Results

You searched for all publications:

Search Again...

Subject Areas (check all that apply) select all

Instruments used to collect data (check all that apply) select all

Collaborations involved (check all that apply) select all

Diamond Offline Facilities used

Relevant Technical Areas (check all that apply) select all

Menu for Anonymous User