Class I histone deacetylases regulate gene transcription and are established therapeutic targets. HDAC1–3 form the catalytic subunit in several distinct multiprotein complexes; however, HDAC inhibitor...

Electrostatic potential surfaces and electric field lines reveal that local fields guide proton delivery through multiple conserved solvent channels in heme peroxidases, enabling efficient access to ....

Actinobacteria are important for industrial production of antibiotics, fine chemicals and food and a source of new compounds for drug discovery. Their central metabolism is regulated by a conserved pr...

[FeFe] hydrogenases are Nature's most efficient catalysts for the cleavage and evolution of molecular hydrogen. Despite decades of research, key aspects of the catalytic cycle and the underlying geome...

Leicester Institute for Structural and Chemical Biology | 51 followers on LinkedIn. Our researchers in chemistry and biology are collaborating to improve our understanding of the workings of life. | T...

Mass spectrometry (MS) is a potentially powerful approach for the diagnostic detection of SARS-CoV-2 and other viruses. However, MS detection is compromised when viral antigens are present at low conc...

The molecular basis for the enrollment of X family DNA polymerases in non-homologous end joining (NHEJ) is unclear. Here the authors elucidate the structure of Pol λ within the DNA-PK long-range compl...

[FeFe]-hydrogenases are highly-active hydrogen-conversion biocatalysts using Earth-abundant metals in their active-site. Understanding their mechanism may enable design of catalysts for renewable ener...

Scientific Reports - Identification and inhibition of PIN1-NRF2 protein–protein interactions through computational and biophysical approaches

Reversible modification of the histone H3 N-terminal tail is critical in regulating the chromatin structure, gene expression, and cell states, while its dysregulation contributes to disease pathogenesis. Understanding the crosstalk between H3 tail modifications in nucleosomes constitutes a central challenge in epigenetics. Here, we describe an engineered sortase transpeptidase, cW11, that displays highly favorable properties for introducing scarless H3 tails onto nucleosomes. This approach significantly accelerates the production of both symmetrically and asymmetrically modified nucleosomes. We demonstrate the utility of asymmetrically modified nucleosomes produced in this way in dissecting the impact of multiple modifications on eraser enzyme processing and molecular recognition by a reader protein. Moreover, we show that cW11 sortase is very effective at cutting and tagging histone H3 tails from endogenous histones, facilitating multiplex “cut-and-paste” middle-down proteomics with tandem mass tags. This cut-and-paste proteomics approach permits the quantitative analysis of histone H3 modification crosstalk after treatment with different histone deacetylase inhibitors. We propose that these chemoenzymatic tail isolation and modification strategies made possible with cW11 sortase will broadly power epigenetic discovery and therapeutic development.