Bicyclic Boronates as Potent Inhibitors of AmpC, the Class C β-Lactamase from Escherichia coli

Autor: Pauline A. Lang, Anete Parkova, Thomas M. Leissing, Karina Calvopiña, Ricky Cain, Alen Krajnc, Tharindi D. Panduwawala, Jules Philippe, Colin W. G. Fishwick, Peteris Trapencieris, Malcolm G. P. Page, Christopher J. Schofield, Jürgen Brem

Publikováno v: Biomolecules, Vol 10, Iss 6, p 899 (2020)

Resistance to β-lactam antibacterials, importantly via production of β-lactamases, threatens their widespread use. Bicyclic boronates show promise as clinically useful, dual-action inhibitors of both serine- (SBL) and metallo- (MBL) β-lactamases.

Externí odkaz: https://doaj.org/article/6ecf02233cc14718992028bf8aa429eb

Anaerobic fixed-target serial crystallography

Autor: Thomas M. Leissing, Pauline A. Lang, Michael A. McDonough, Bradley Davy, Robin L. Owen, Stephen B. Carr, Patrick Rabe, Julien Orlans, Pierre Aller, Anna Dirr, Allen M. Orville, Selina L. S. Storm, Christopher J. Schofield, A. Ebrahim, Danny Axford, John H. Beale, A. Butryn

Publikováno v: IUCrJ
International Union of Crystallography journal
International Union of Crystallography journal, International Union of Crystallography 2020, 7 (5), pp.901-912. ⟨10.1107/S2052252520010374⟩
IUCrJ, Vol 7, Iss 5, Pp 901-912 (2020)

An effective and simple-to-implement approach for anaerobic room-temperature data collection is described and demonstrated by application to dioxygen utilizing enzymes.
Cryogenic X-ray diffraction is a powerful tool for crystallographic studies

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::92b29884b169f66b92b853144548fd0b
http://europepmc.org/articles/PMC7467159

Imitation of β-lactam binding enables broad-spectrum metallo-β-lactamase inhibitors

Autor: Jürgen Brem, Tharindi Panduwawala, Jon Ulf Hansen, Joanne Hewitt, Edgars Liepins, Pawel Donets, Laura Espina, Alistair J. M. Farley, Kirill Shubin, Gonzalo Gomez Campillos, Paula Kiuru, Shifali Shishodia, Daniel Krahn, Robert K. Leśniak, Juliane Schmidt, Karina Calvopiña, María-Carmen Turrientes, Madeline E. Kavanagh, Dmitrijs Lubriks, Philip Hinchliffe, Gareth W. Langley, Ali F. Aboklaish, Anders Eneroth, Maria Backlund, Andrei G. Baran, Elisabet I. Nielsen, Michael Speake, Janis Kuka, John Robinson, Solveiga Grinberga, Lindsay Robinson, Michael A. McDonough, Anna M. Rydzik, Thomas M. Leissing, Juan Carlos Jimenez-Castellanos, Matthew B. Avison, Solange Da Silva Pinto, Andrew D. Pannifer, Marina Martjuga, Emma Widlake, Martins Priede, Iva Hopkins Navratilova, Marek Gniadkowski, Anna Karin Belfrage, Peter Brandt, Jari Yli-Kauhaluoma, Eric Bacque, Malcolm G. P. Page, Fredrik Björkling, Jonathan M. Tyrrell, James Spencer, Pauline A. Lang, Pawel Baranczewski, Rafael Cantón, Stuart P. McElroy, Philip S. Jones, Fernando Baquero, Edgars Suna, Angus Morrison, Timothy R. Walsh, Christopher J. Schofield

Publikováno v: Brem, J, Panduwawala, T, Hansen, J U, Hewitt, J, Liepins, E, Donets, P, Espina, L, Farley, A J M, Shubin, K, Campillos, G G, Kiuru, P, Shishodia, S, Krahn, D, Leśniak, R K, Schmidt Adrian, J, Calvopiña, K, Turrientes, M-C, Kavanagh, M E, Lubriks, D, Hinchliffe, P, Langley, G W, Aboklaish, A F, Eneroth, A, Backlund, M, Baran, A G, Nielsen, E I, Speake, M, Kuka, J, Robinson, J, Grinberga, S, Robinson, L, McDonough, M A, Rydzik, A M, Leissing, T M, Jimenez-Castellanos, J C, Avison, M B, Da Silva Pinto, S, Pannifer, A D, Martjuga, M, Widlake, E, Priede, M, Hopkins Navratilova, I, Gniadkowski, M, Belfrage, A K, Brandt, P, Yli-Kauhaluoma, J, Bacque, E, Page, M G P, Björkling, F, Tyrrell, J M, Spencer, J, Lang, P A, Baranczewski, P, Cantón, R, McElroy, S P, Jones, P S, Baquero, F, Suna, E, Morrison, A, Walsh, T R & Schofield, C J 2022, ' Imitation of β-lactam binding enables broad-spectrum metallo-β-lactamase inhibitors ', Nature Chemistry, vol. 14, pp. 15-24 . https://doi.org/10.1038/s41557-021-00831-x

Carbapenems are vital antibiotics, but their efficacy is increasingly compromised by metallo-beta-lactamases (MBLs). Here we report the discovery and optimization of potent broad-spectrum MBL inhibitors. A high-throughput screen for NDM-1 inhibitors

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3b4fafe7a19ff7ed314c37086b73a558
https://research-information.bris.ac.uk/ws/files/323318874/IC_MBLinh_NatChem_accepted.pdf

Structural Investigations of the Inhibition of Escherichia coli AmpC β-Lactamase by Diazabicyclooctanes

Autor: Malcolm G. P. Page, Jürgen Brem, Christopher J. Schofield, Thomas M. Leissing, Pauline A. Lang

Publikováno v: Antimicrobial Agents and Chemotherapy

β-Lactam antibiotics are presently the most important treatments for infections by pathogenic Escherichia coli, but their use is increasingly compromised by β-lactamases, including the chromosomally encoded class C AmpC serine-β-lactamases (SBLs).

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::deaeceddf3b0fa03a70ed27b7e403c5a
https://doi.org/10.1128/aac.02073-20

A human protein hydroxylase that accepts D-residues

Autor: Wei Ge, Christopher J. Schofield, Michael A. McDonough, John S. Scotti, Yu Nakashima, Hwangseo Park, Marios S. Markoulides, Hwanho Choi, Rasheduzzaman Chowdhury, Helen Thorbjornsrud, Joongoo Lee, Dahye Kang, Sungwoo Hong, Thomas M. Leissing, Philip A. Gerken, Adam P. Hardy

Publikováno v: Communications Chemistry, Vol 3, Iss 1, Pp 1-10 (2020)

Factor inhibiting hypoxia-inducible factor (FIH) is a 2-oxoglutarate-dependent protein hydroxylase that catalyses C3 hydroxylations of protein residues. We report FIH can accept (D)- and (L)-residues for hydroxylation. The substrate selectivity of FI

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e89995fd45c2e033b823838675872fdc
https://doi.org/10.1038/s42004-020-0290-5