Accès ouvert
2026
article
OpenAlex
Chris Williams, Laura M. Nocka, George Hedger, Pragya Parashara et autres
Receptor-type E3 ubiquitin ligases enable extracellular signals to control ubiquitylation in the cytoplasm, playing widespread roles in development, metabolism, and immunity. Using cryoelectron microscopy, integrated with biophysical and functional studies, we visualized a human E3 complex composed of two transmembrane proteins, MEGF8 …
gb, us, bd, be, cz
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Accès ouvert
2026
article
OpenAlex
Douglas S. M. Ferreira, Katie McLennan, M. Vollmar, W. Kiyani et autres
Human methionine synthase (MTR) is an essential enzyme of one carbon metabolism. Consisting of a catalytic N-half and a cobalamin binding C-half, MTR utilises this intricate organometallic cofactor in the methyl transfer from methyltetrahydrofolate to homocysteine producing methionine. Cobalamin loading into MTR, …
gb, ch, de, se, us
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Accès ouvert
2026
preprint
OpenAlex
Wei Song, J.A. Newman, Yichen Zhao, R. Chalk et autres
The DNA-dependent metalloprotease SPRTN has emerged as a key enzyme in the proteolysis of DNA-protein crosslinks (DPCs), thereby protecting us against genome instability, accelerated ageing, and cancer. DNA and ubiquitin chains serve as the primary activator and catalyst of SPRTN proteolysis, respectively, …
gb, sg
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Accès ouvert
2025
article
OpenAlex
Eva Kot, Matteo P. Ferla, Patricia Helen Hollinshead, Charles W.E. Tomlinson et autres
Abstract BACKGROUND In order to alleviate the growing issue of herbicide resistance, diversification of the herbicide portfolio is necessary. A promising yet underutilized mode‐of‐action is the inhibition of fatty acid thioesterases (FATs), which terminate de novo fatty acid (FA) biosynthesis by releasing …
ca, gb, ch, Afrique du Sud
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Accès ouvert
2024
article
OpenAlex
Imre Fejes, Piroska Markacz, János Tatai, Mónika Rudas et autres
The NRF2-KEAP1 interaction is central for cytoprotection against stresses, giving it high clinical significance. Covalent modification of KEAP1 is an efficient approach, but the covalent inhibitors used in the clinic carry undesired side effects originating in their moderate selectivity. Starting with a …
fr, kh, gb
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Accès ouvert
2024
article
OpenAlex
Tomas C. Pascoa, A.C.W. Pike, Christofer S. Tautermann, Gamma Chi et autres
Ceramides are bioactive sphingolipids crucial for regulating cellular metabolism. Ceramides and dihydroceramides are synthesized by six ceramide synthase (CerS) enzymes, each with specificity for different acyl-CoA substrates. Ceramide with a 16-carbon acyl chain (C16 ceramide) has been implicated in obesity, insulin resistance …
gb, de, ch
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Accès ouvert
2024
article
OpenAlex
Hang Fu, Katis V.L., Axtman A.D., Cary G.A. et autres
RNA sequencing and genetic data support spleen tyrosine kinase (SYK) and high affinity immunoglobulin epsilon receptor subunit gamma (FCER1G) as putative targets to be modulated for Alzheimer’s disease (AD) therapy. FCER1G is a component of Fc receptor complexes that contain an immunoreceptor …
us
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Accès ouvert
2024
article
OpenAlex
Frances M. Bashore, V.L. Katis, Yuhong Du, Arunima Sikdar et autres
RNA sequencing and genetic data support spleen tyrosine kinase (SYK) and high affinity immunoglobulin epsilon receptor subunit gamma (FCER1G) as putative targets to be modulated for Alzheimer's disease (AD) therapy. FCER1G is a component of Fc receptor complexes that contain an immunoreceptor …
us, gb
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Accès ouvert
2024
article
OpenAlex
W.J. Bradshaw, Emma C. Kennedy, Tiago Moreira, Luke Smith et autres
SHIP1, an inositol 5-phosphatase, plays a central role in cellular signaling. As such, it has been implicated in many conditions. Exploiting SHIP1 as a drug target will require structural knowledge and the design of selective small molecules. We have determined apo, and …
gb
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Accès ouvert
2024
article
OpenAlex
Kerry A. Miller, David A. Cruz Walma, Daniel M. Pinkas, Rebecca S Tooze et autres
Introduction KCTD15 encodes an oligomeric BTB domain protein reported to inhibit neural crest formation through repression of Wnt/beta-catenin signalling, as well as transactivation by TFAP2. Heterozygous missense variants in the closely related paralogue KCTD1 cause scalp-ear-nipple syndrome. Methods Exome sequencing was performed …
gb, us, es
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Accès ouvert
2023
preprint
OpenAlex
Tomas C. Pascoa, A.C.W. Pike, Christofer S. Tautermann, Gamma Chi et autres
Abstract Ceramides are bioactive sphingolipids that play pivotal roles in regulating cellular metabolism. Ceramides and dihydroceramides are synthesized by a family of six ceramide synthase enzymes (CerS), each with distinct specificity for the acyl-CoA substrate. Importantly, the acyl chain length plays a …
gb, de, ch
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Accès ouvert
2023
article
OpenAlex
Gamma Chi, Larissa Dietz, Haiping Tang, M. Snee et autres
In this study, we present the structures of human urea transporters UT-A and UT-B to characterize them at molecular level and to detail the mechanism of UT-B inhibition by its selective inhibitor, UTB inh -14. High-resolution structures of both transporters establish the …
gb, be
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