Structural basis for CCR6 modulation by allosteric antagonists

Autor: David Jonathan Wasilko, Brian S. Gerstenberger, Kathleen A. Farley, Wei Li, Jennifer Alley, Mark E. Schnute, Ray J. Unwalla, Jorge Victorino, Kimberly K. Crouse, Ru Ding, Parag V. Sahasrabudhe, Fabien Vincent, Richard K. Frisbie, Alpay Dermenci, Andrew Flick, Chulho Choi, Gary Chinigo, James J. Mousseau, John I. Trujillo, Philippe Nuhant, Prolay Mondal, Vincent Lombardo, Daniel Lamb, Barbara J. Hogan, Gurdeep Singh Minhas, Elena Segala, Christine Oswald, Ian W. Windsor, Seungil Han, Mathieu Rappas, Robert M. Cooke, Matthew F. Calabrese, Gabriel Berstein, Atli Thorarensen, Huixian Wu

Publikováno v: Nature Communications, Vol 15, Iss 1, Pp 1-13 (2024)

Abstract The CC chemokine receptor 6 (CCR6) is a potential target for chronic inflammatory diseases. Previously, we reported an active CCR6 structure in complex with its cognate chemokine CCL20, revealing the molecular basis of CCR6 activation. Here,

Externí odkaz: https://doaj.org/article/91af6bd491994266b492f68b0994ea6e

From structure to clinic: design of a muscarinic M1 receptor agonist with the potential to treat Alzheimer’s disease

Autor: Andrew B. Tobin, Gerard R. Dawson, Patrick M. Sexton, Nathan Robertson, Sophie J. Bradley, Francesca Perini, Arthur Christopoulos, James C. Errey, Barry John Teobald, John Francis William Deakin, Lisa M. Broad, Jan Liptrot, Christopher J. Langmead, K.A. Bennett, Mary Vinson, Pradeep J. Nathan, Colin Molloy, Robert M. Cooke, Edward Hurrell, Michael Browning, Krzysztof Okrasa, Jason M Brown, Giulio Mattedi, Alastair J. H. Brown, David M. Cross, Greg J. Osborne, Julie E. Cansfield, Ali Jazayeri, Christoffer Bundgaard, Stephen R. Morairty, J.C. Patel, Fiona H. Marshall, Brian D. Hudson, Prakash Rucktooa, Robert T. Smith, Keith G. Phillips, Louis Dwomoh, Chris de Graaf, Malcolm Peter Weir, Julie Warneck, Giles A. Brown, Mark Pickworth, Benjamin G. Tehan, Tim Tasker, Anushka V. Goonawardena, Miles Congreve, João M. Dias, Shahram Shahabi

Current therapies for Alzheimer's disease seek to correct for defective cholinergic transmission by preventing the breakdown of acetylcholine through inhibition of acetylcholinesterase, these however have limited clinical efficacy. An alternative app

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0b008b7a3c01abe25b8e63fdab465cc4
https://ora.ox.ac.uk/objects/uuid:fc10e298-8675-4411-9af5-3cfd801f0d78

X‐Ray Crystallography and Free Energy Calculations Reveal the Binding Mechanism of A 2A Adenosine Receptor Antagonists

Autor: María Majellaro, Robert M. Cooke, Andrei Zhukov, Andrew S. Doré, Francesca Deflorian, Henrik Keränen, Hugo Gutiérrez-de-Terán, Grégory Verdon, Miles Congreve, Johan Åqvist, Eddy Sotelo, Jhonny Azuaje, Xerardo García-Mera, Chris de Graaf, Willem Jespers, Jonathan S. Mason

Publikováno v: Angewandte Chemie (International Ed. in English)
Minerva: Repositorio Institucional de la Universidad de Santiago de Compostela
Universidad de Santiago de Compostela (USC)
Minerva. Repositorio Institucional de la Universidad de Santiago de Compostela
instname

We present a robust protocol based on iterations of free energy perturbation (FEP) calculations, chemical synthesis, biophysical mapping and X‐ray crystallography to reveal the binding mode of an antagonist series to the A2A adenosine receptor (AR)

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1fb82a0e9f21ff3cb50f65224bd63c71
https://doi.org/10.1002/anie.202003788

Crystal structure and subsequent ligand design of a nonriboside partial agonist bound to the adenosine A2A receptor

Autor: Tasia Amelia, Robert K. Y. Cheng, Gerard J. P. van Westen, Rongfang Liu, Elena Segala, Robert M. Cooke, Laura H. Heitman, Jacobus P. D. van Veldhoven, Daan van der Es, Matteo Falsini, Grégory Verdon, Adriaan P. IJzerman

Publikováno v: Journal of Medicinal Chemistry, 64(7), 3827-3842. American Chemical Society (ACS)
Journal of Medicinal Chemistry

In this study, we determined the crystal structure of an engineered human adenosine A2A receptor bound to a partial agonist and compared it to structures cocrystallized with either a full agonist or an antagonist/inverse agonist. The interaction betw

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a3eaee9ee24339f7b4772a78e3323223
http://hdl.handle.net/1887/3204468

From structure to clinic: Design of a muscarinic M1 receptor agonist with potential to treatment of Alzheimer's disease

Autor: Alastair J H, Brown, Sophie J, Bradley, Fiona H, Marshall, Giles A, Brown, Kirstie A, Bennett, Jason, Brown, Julie E, Cansfield, David M, Cross, Chris, de Graaf, Brian D, Hudson, Louis, Dwomoh, João M, Dias, James C, Errey, Edward, Hurrell, Jan, Liptrot, Giulio, Mattedi, Colin, Molloy, Pradeep J, Nathan, Krzysztof, Okrasa, Greg, Osborne, Jayesh C, Patel, Mark, Pickworth, Nathan, Robertson, Shahram, Shahabi, Christoffer, Bundgaard, Keith, Phillips, Lisa M, Broad, Anushka V, Goonawardena, Stephen R, Morairty, Michael, Browning, Francesca, Perini, Gerard R, Dawson, John F W, Deakin, Robert T, Smith, Patrick M, Sexton, Julie, Warneck, Mary, Vinson, Tim, Tasker, Benjamin G, Tehan, Barry, Teobald, Arthur, Christopoulos, Christopher J, Langmead, Ali, Jazayeri, Robert M, Cooke, Prakash, Rucktooa, Miles S, Congreve, Malcolm, Weir, Andrew B, Tobin

Publikováno v: Trends Pharmacol Sci

Current therapies for Alzheimer's disease seek to correct for defective cholinergic transmission by preventing the breakdown of acetylcholine through inhibition of acetylcholinesterase, these however have limited clinical efficacy. An alternative app

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=pmid________::7763e10dd2dc92975133618856c2920a
https://pubmed.ncbi.nlm.nih.gov/35101279