391 papers
By developing the GATO-seq assay and utilizing cryo-EM, this study reveals that a specific nucleic acid sequence induces a unique, TFIIIS-resistant "super pause" in RNA polymerase II, which stabilizes a reversible, single-nucleotide backtracked "sidetracked" state through a threonine-lined pocket, thereby demonstrating how sequence directly encodes transcriptional pausing control.
This study deciphers and demonstrates the engineerability of a structural code governing the picomolar-affinity, sequence-specific CRA-CRA pairing that dictates the precise assembly of GID/CTLH-type E3 ligases, enabling the reprogramming of their subunit interactions.
This study introduces highly sensitive and rapid chemiluminescent probes that selectively target the ClbP enzyme, enabling the direct detection of colibactin-producing *E. coli* in complex stool samples for applications in cancer research and clinical screening.
This study presents a comprehensive structural analysis of 345 NADH-protein complexes using a descriptor-driven approach to reveal that NADH conformation is largely conserved with a specific adenine-nicotinamide separation, while its recognition is dominated by hydrogen bonding and electrostatic interactions centered on the nicotinamide region, thereby establishing a unified biophysical framework for cofactor engineering and inhibitor design.
This study demonstrates that commutable reference materials derived from healthy donor serum, calibrated against an LC-MS/MS method, can successfully harmonize diverse IGF1 immunoassays and enable the establishment of unified age-related reference intervals.
This study utilizes activity-based protein profiling to map ligandable cysteines in the wheat pathogen *Zymoseptoria tritici*, identifying a specific ortholog-restricted cysteine in the essential GTPase SAR1 that can be selectively targeted by stereoprobes to inhibit fungal growth and offer a new strategy for combating drug-resistant Septoria tritici leaf blotch.
The crystal structure of the H158Y mutant of pyranose oxidase reveals that the substitution of His158 with Tyr158 prevents covalent flavinylation due to an incompatible rotamer conformation stabilized by a hydrogen bond with Lys79, resulting in a significant loss of catalytic activity despite retained FAD occupancy and tetrameric assembly.
By combining classical and QM/MM molecular dynamics simulations, this study elucidates the complete mechanistic framework of spliceostatin reactivity, revealing how local distortion of the PHF5A zinc finger's coordination sphere generates a reactive thiolate and how a specific proton relay accelerates epoxide ring opening to enable covalent inhibition of the spliceosome.
The authors present Enzyme-toolkit (Enzyme-tk), a unified pipeline integrating 23 open-source tools and two novel methods (Func-e and Oligopoolio) to discover previously unknown enzymes for specific reactions, successfully identifying thermostable candidates capable of degrading man-made pollutants like DEHP and TPP.
This study reveals that condensin II activation during mitosis operates via a bipartite mechanism where the protein M18BP1 both relieves autoinhibition by the NCAPD3 tail and directly enhances DNA anchoring through a positively charged loop, thereby enabling stable chromosome organization.