A high-throughput MALDI-TOF MS biochemical screen for small molecule inhibitors of the antigen aminopeptidase ERAP1

Autor: Leonie Müller, Amy K Burton, Chloe L Tayler, James E Rowedder, Jonathan P Hutchinson, Simon Peace, Julie M Quayle, Melanie V Leveridge, Roland S Annan, Matthias Trost, Rachel E Peltier-Heap, Maria Emilia Dueñas

Publikováno v: SLAS Discovery, Vol 28, Iss 1, Pp 3-11 (2023)

MALDI-TOF MS is a powerful analytical technique that provides a fast and label-free readout for in vitro assays in the high-throughput screening (HTS) environment. Here, we describe the development of a novel, HTS compatible, MALDI-TOF MS-based drug

Externí odkaz: https://doaj.org/article/c0f8fd18f1724d62b41a5843c6740ea7

Structural and mechanistic basis of differentiated inhibitors of the acute pancreatitis target kynurenine-3-monooxygenase

Autor: Jonathan P. Hutchinson, Paul Rowland, Mark R. D. Taylor, Erica M. Christodoulou, Carl Haslam, Clare I. Hobbs, Duncan S. Holmes, Paul Homes, John Liddle, Damian J. Mole, Iain Uings, Ann L. Walker, Scott P. Webster, Christopher G. Mowat, Chun-wa Chung

Publikováno v: Nature Communications, Vol 8, Iss 1, Pp 1-12 (2017)

Kynurenine-3-monooxygenase (KMO) is an emerging clinical target for treatment of neurodegenerative diseases and acute pancreatitis. Here, the authors report potent inhibitors that bind KMO in an unexpected conformation, offering structural and mechan

Externí odkaz: https://doaj.org/article/6a2d1e05cbf54050aa6e26f4834e4b9a

Common allotypes of ER aminopeptidase 1 have substrate-dependent and highly variable enzymatic properties

Autor: Semra Kitchen, Efstratios Stratikos, Ioannis Temponeras, Jonas J.W. Kuiper, Adrian Cortes, Jonathan P. Hutchinson, Justyna Korczynska

Publikováno v: The Journal of Biological Chemistry

ObjectivePolymorphic variation of immune system proteins can drive variability of individual immune responses. ER aminopeptidase 1 (ERAP1) generates antigenic peptides for presentation by MHC class I molecules. Coding single nucleotide polymorphisms

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6323837b8dde7493a20ba074d0958941
https://doi.org/10.1101/2020.11.19.389403

Targeting the Regulatory Site of ER Aminopeptidase 1 Leads to the Discovery of a Natural Product Modulator of Antigen Presentation

Autor: Jonathan D Lea, Robert J. Young, Duncan S. Holmes, Christopher P. Tinworth, Jonathan P. Hutchinson, Semra Kitchen, Justyna Wojno-Picon, Leng Nickels, Michelle Pemberton, Hester Sheehan, Justyna Korczynska, Margarete Neu, Jessica L. Schneck, Efstratios Stratikos, Despoina Koumantou, Iain Uings, Ted Cecconie, Alex Phillipou, Emma J. Jones, John Liddle, Paul Rowland

Publikováno v: Journal of medicinal chemistry. 63(6)

ER aminopeptidase 1 (ERAP1) is an intracellular enzyme that generates antigenic peptides and is an emerging target for cancer immunotherapy and the control of autoimmunity. ERAP1 inhibitors described previously target the active site and are limited

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e9a308daba45dd112f8cbd5048d0a1cc
https://pubmed.ncbi.nlm.nih.gov/32109056

Structural and mechanistic basis of differentiated inhibitors of the acute pancreatitis target kynurenine-3-monooxygenase

Autor: Duncan S. Holmes, Paul Homes, Chun-wa Chung, Ann Louise Walker, Jonathan P. Hutchinson, Erica Christodoulou, John Liddle, Christopher G. Mowat, Scott P. Webster, Iain Uings, Carl Haslam, Clare I. Hobbs, Damian J. Mole, Paul Rowland, Mark R D Taylor

Publikováno v: Nature Communications, Vol 8, Iss 1, Pp 1-12 (2017)
Hutchinson, J P, Rowland, P, Taylor, M R D, Christodoulou, E M, Haslam, C, Hobbs, C M, Holmes, D, Homes, P, Liddle, J, Mole, D J, Uings, I J, Walker, A L, Webster, S P, Mowat, C & Chung, C 2017, ' Structural and mechanistic basis of differentiated inhibitors of the acute pancreatitis target kynurenine-3-monooxygenase ', Nature Communications, vol. 8, 15827 . https://doi.org/10.1038/ncomms15827
Nature Communications
'Nature Communications ', vol: 8, pages: 15827-1-15827-12 (2017)

Kynurenine-3-monooxygenase (KMO) is a key FAD-dependent enzyme of tryptophan metabolism. In animal models, KMO inhibition has shown benefit in neurodegenerative diseases such as Huntington's and Alzheimer's. Most recently it has been identified as a

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c7052eaed51497ed8d9f669cdc0a94bd
https://doaj.org/article/6a2d1e05cbf54050aa6e26f4834e4b9a