2025年2月27日 · We show that TIGR arrays are processed into 36-nt RNAs (tigRNAs) that direct sequence-specific DNA binding through a tandem-spacer targeting mechanism. TasR can be reprogrammed for precise DNA cleavage, including in human cells.

2025年2月27日 · We show that TIGR arrays are processed into 36-nt RNAs (tigRNAs) that direct sequence-specific DNA binding through a tandem-spacer targeting mechanism. TasR can be reprogrammed for precise DNA cleavage, including in human cells.

2022年1月11日 · FIIN-2, TAS-120 (Futibatinib) and PRN1371 are highly potent pan-FGFR covalent inhibitors targeting the p-loop cysteine of FGFR proteins, of which TAS-120 and PRN1371 are currently in clinical...

2019年2月19日 · We hypothesise that the most significant reactivity feature of TAS-120 is its inherent ability to undertake conformational sampling of the FGFR P-loop. In designing novel covalent FGFR inhibitors, such a phenomenon presents an attractive strategy requiring appropriate positioning of an acrylamide group similarly to that of TAS-120.

2025年2月27日 · Zhang’s team discovered more than 20,000 different Tas proteins, mostly occurring in bacteria-infecting viruses. Sequences within each gene’s repetitive region — its TIGR arrays — encode an RNA guide that interacts with the RNA-binding part of the protein. In some, the RNA-binding region is adjacent to a DNA-cutting part of the protein.

2019年1月2日 · Free ligand, reversible, and irreversible structures show each step of the covalent modification of the target. We propose that TAS-120 samples a multitude of conformations of the highly flexible P-loop in the target kinases.

TAS-120 was designed to overcome FGFR kinase domain mutations, taking advantage of the improved potency and specificity afforded by its covalent binding mode and distinct orientation in the ATP-binding pocket of FGFRs.

We reveal a small-molecule crystal struc-ture of the free ligand, and both reversible and irreversible binding in FGFR1, providing coverage of the full range of drug conformations and binding interactions, and the features that afford high …

Here, we report the use of a novel in vivo randomization and selection strategy to identify a Tas DNA binding site consensus. This approach takes advantage of the fact that Tas can effectively activate gene expression in yeast cells via a Tas DNA binding site derived from the simian foamy virus type 1 (SFV-1) internal promoter.

2006年8月8日 · Toxin-antitoxin systems (TAS) are abundant, diverse, horizontally mobile gene modules that encode powerful resistance mechanisms in prokaryotes. We use the comparative-genomic approach to predict a new TAS that consists of a two-gene cassette encoding uncharacterized HicA and HicB proteins.