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Plant Cell 2021 Jan 25. Epub 2021 Jan 25.

Department of Plant Biotechnology and Bioinformatics, Ghent University, Technologiepark 71, 9052 Ghent, Belgium.

Identifying protein-protein interactions (PPIs) is crucial for understanding biological processes. Many PPI tools are available, yet only some function within the context of a plant cell. Narrowing down even further, only a few tools allow complex multi-protein interactions to be visualized. Read More

Molecules 2021 Feb 19;26(4). Epub 2021 Feb 19.

Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Palatucci 13, I-98168 Messina, Italy.

Computer aided drug-design methods proved to be powerful tools for the identification of new therapeutic agents. We employed a structure-based workflow to identify new inhibitors targeting mTOR kinase at rapamycin binding site. By combining molecular dynamics (MD) simulation and pharmacophore modelling, a simplified structure-based pharmacophore hypothesis was built starting from the FKBP12-rapamycin-FRB ternary complex retrieved from RCSB Protein Data Bank (PDB code 1FAP). Read More

Adv Sci (Weinh) 2021 Feb 13;8(3):2002148. Epub 2020 Dec 13.

Center for Translational Cancer Research Institute of Biosciences and Technology Texas A&M University Houston TX 77030 USA.

A genetically encoded caffeine-operated synthetic module (COSMO) is introduced herein as a robust chemically induced dimerization (CID) system. COSMO enables chemogenetic manipulation of biological processes by caffeine and its metabolites, as well as caffeinated beverages, including coffee, tea, soda, and energy drinks. This CID tool, evolved from an anti-caffeine nanobody via cell-based high-throughput screening, permits caffeine-inducible gating of calcium channels, tumor killing via necroptosis, growth factors-independent activation of tyrosine receptor kinase signaling, and enhancement of nanobody-mediated antigen recognition for the severe acute respiratory distress coronavirus 2 (SARS-CoV-2) spike protein. Read More

iScience 2020 Sep 6;23(9):101533. Epub 2020 Sep 6.

Department of Chemistry, University of Illinois at Chicago, Chicago, IL, USA.

Lanthanide-based, Förster resonance energy transfer (LRET) biosensors enabled sensitive, time-gated luminescence (TGL) imaging or multiwell plate analysis of protein-protein interactions (PPIs) in living cells. We prepared stable cell lines that expressed polypeptides composed of an alpha helical linker flanked by a Tb(III) complex-binding domain, GFP, and two interacting domains at each terminus. The PPIs examined included those between FKBP12 and the rapamycin-binding domain of m-Tor (FRB) and between p53 (1-92) and HDM2 (1-128). Read More

Appl Microbiol Biotechnol 2020 Nov 17;104(21):9125-9134. Epub 2020 Sep 17.

State Key Laboratory of Microbial Technology, Institute of Microbial Technology, Shandong University, Qingdao, 266237, People's Republic of China.

The macrolactone rapamycin (RAP) presents a broad range of bioactivities, but its clinical applications are compromised due to the poor water solubility and low bioavailability, which could probably be overcome by glycosylation. In this study, we tested a set of promiscuous glycosyltransferases (GTs) to modify rapamycin with four different sugar donors. BsGT-1 displayed the best glycosylation activity with a preference for UDP-glucose, and the glycosylation happened at C-28 or C-40 of rapamycin, producing rapamycin-40-O-β-D-glucoside (RG1), and two new compounds rapamycin-28-O-β-D-glucoside (RG2) and rapamycin-28,40-O-β-D-diglucoside (RG3). Read More