Jing Yang Similar Datasets
Project description:Advances in the synthesis and screening of small-molecule libraries have accelerated the discovery of chemical probes for studying biological processes. Still, only a small fraction of the human proteome has chemical ligands, and the full complement of proteins with potential to be targeted by small molecules remains unknown. Here, we describe a platform that marries fragment-based ligand discovery with quantitative chemical proteomics to map thousands of reversible small molecule-protein interactions directly in human cells, many of which can be site-specifically determined. We advance this knowledge to create ligands that affect the activity of proteins heretofore lacking chemical probes and to identify by phenotypic screening small molecules that promote adipocyte differentiation by engaging the poorly characterized membrane protein PGRMC2. Fragment-based screening in human cells thus provides an extensive proteome-wide map of protein ligandability and facilitates the coordinated discovery of bioactive small molecules and their molecular targets.
2017-01-24 | GSE90731 | GEO
Project description:Chemical modulation of protein function enables a mechanistic understanding of biological circuits and represents the foundation of most medicines. However, despite major efforts over decades of research, around 80% of the human proteome still lack functional ligands. Chemical proteomics allowed the advancement of fragment-based ligand discovery (FBLD) towards cellular systems and emerged as a promising strategy to detect reversible fragment-protein interactions that can be furnished into bioactive chemical probes. Limitations in scale and throughput have, however, stymied the interpretation of the resulting ligandability maps, thus complicating the identification of specific and actionable fragment-protein interactions. Here, we report reversible, global ligandability maps for 435 structurally different fragments, collectively representing 6739 discrete interactions. We benchmark the dataset by showing that identified fragments can be advanced to active chemical probes. Integrating multi-layered ligandability portraits with artificial intelligence (AI) and machine learning (ML) enabled quantitative and qualitative predictions of fragment interactomes via chemically interpretable models. The resulting, interactive catalogue of fragment-protein interactions and predictive models is expected to expedite ligand discovery efforts in a community-wide fashion and should facilitate the pursuit of hitherto undrugged target proteins.
2024-05-07 | PXD041587 | Pride
Project description: Not available
| S-EPMC16870 | biostudies-literature
Project description:Thiol-dependent redox regulation is essential for the rapid adaptation of chloroplast metabolism to unpredictable changes of light intensity. The disulfide reductase activity of thioredoxins (Trxs), which relies on photo-reduced ferredoxin (Fdx) and a Fdx-dependent Trx reductase (FTR), constitutes the Fdx-FTR-Trxs system, which links chloroplast redox regulation to light. In addition, chloroplasts harbor an NADPH-dependent Trx reductase (NTR) with a joint Trx domain, NTRC. The activity of these two redox systems is integrated by the balance of the hydrogen peroxide scavenging enzyme 2-Cys peroxiredoxin (2-Cys Prx), which thus plays a key role in maintaining the reducing capacity of chloroplast Trxs in response to light intensity. Based on the severe phenotype of mutant lines lacking NTRC, it is clear that this enzyme plays an essential role in chloroplast redox homeostasis. However, whether the function of NTRC depends on its capacity of reduce 2-Cys Prxs or has additional targets remains unknown. Here, we have addressed this issue by a comparative analysis of the triple mutant of Arabidopsis thaliana, ntrc-2cpab, simultaneously lacking 2-Cys Prxs and NTRC, and the double mutant 2cpab lacking 2-Cys Prxs. The phenotype of the ntrc-2cpab mutant is indistinguishable of the 2cpab mutant, as shown by growth rate, photosynthesis performance, light-dependent redox regulation of enzyme activity and comparative transcriptomics based RNA-Seq. Based on these results, we propose that the function of NTRC in chloroplast redox homeostasis is exerted by the regulation of the redox balance of 2-Cys Prxs rather than by the direct reduction of additional targets.
2021-09-09 | GSE147793 | GEO
Project description: Not available
| S-EPMC4646424 | biostudies-literature
Project description:The binding of serum immunoglobulins to proteins was compared using serum from after and before an immunotherapeutic intervention (donor lymphocyte infusion) in two patients who had relapsed chronic lymphocytic leukemia (CLL) after bone marrow transplant. One Invitrogen ProtoArray was used for each sample. Significant interactions were determined by comparing the before and after samples for each patient separately, using the Concentration-Dependent Analysis described in Marina et al., J Proteome Res, 2008. One sample from before and one sample from after immunotherapy were tested for each patient. Keywords: Immune response discovery
2008-05-31 | GSE11564 | GEO
Project description:The binding of serum immunoglobulins to proteins was compared using serum from after and before an immunotherapeutic intervention (donor lymphocyte infusion) in two patients who had relapsed chronic lymphocytic leukemia (CLL) after bone marrow transplant. One Invitrogen ProtoArray was used for each sample. Significant interactions were determined by comparing the before and after samples for each patient separately, using the Concentration-Dependent Analysis described in Marina et al., J Proteome Res, 2008. One sample from before and one sample from after immunotherapy were tested for each patient. Keywords: Immune response discovery One sample from before and one sample from after immunotherapy were tested for each patient.
2008-05-31 | E-GEOD-11564 | biostudies-arrayexpress
Project description:The cellular redox status plays an essential role in diverse cellular functions, including proliferation, protein homeostasis, and aging. Thus even cells with identical genetic background but different redox status behave differently. Here, we propose a non-laborious and robust methodology to quantify cell-to- cell redox-dependent variability within thousands of cells, detect oxidation levels in cytosol, mitochondria, and peroxisome, and sort cells based on their redox status. We report that cells of the same age have a bi-modular distribution of reduced and oxidized cells starting in the late logarithmic phase. Although the ratio between the oxidized and reduced subpopulations changes during chronological aging, their growth, proteomic and transcriptomic features are conserved during their first days of chronological aging. A comparative proteomic analysis identified three key proteins, Hsp30, Dhh1, and Pnc1, which affect basal oxidation levels and may serve as first line of defense proteins in redox homeostasis.
2018-06-17 | GSE112997 | GEO
Project description: Not available
| S-EPMC4594084 | biostudies-literature
Project description: Not available
| S-EPMC5750842 | biostudies-other