7 research outputs found
Changes in NLR and PSA response rate at 12weeks.
<p>Changes in NLR and PSA response rate at 12weeks.</p
Overall survival according to pre-therapy and follow-up NLR at 4 weeks of enzalutamide treatment.
<p>Overall survival according to pre-therapy and follow-up NLR at 4 weeks of enzalutamide treatment.</p
Progression-free survival according to pre-therapy and follow-up NLR at 4 weeks of enzalutamide treatment.
<p>Progression-free survival according to pre-therapy and follow-up NLR at 4 weeks of enzalutamide treatment.</p
Protein Recognition by Short Peptide Reversible Inhibitors of the Chromatin-Modifying LSD1/CoREST Lysine Demethylase
The
combinatorial assembly of protein complexes is at the heart
of chromatin biology. Lysine demethylase LSD1Â(KDM1A)/CoREST beautifully
exemplifies this concept. The active site of the enzyme tightly associates
to the N-terminal domain of transcription factors of the SNAIL1 family,
which therefore can competitively inhibit the binding of the N-terminal
tail of the histone substrate. Our enzymatic, crystallographic, spectroscopic,
and computational studies reveal that LSD1/CoREST can bind to a hexapeptide
derived from the SNAIL sequence through recognition of a positively
charged α-helical turn that forms upon binding to the enzyme.
Variations in sequence and length of this six amino acid ligand modulate
affinities enabling the same binding site to differentially interact
with proteins that exert distinct biological functions. The discovered
short peptide inhibitors exhibit antiproliferative activities and
lay the foundation for the development of peptidomimetic small molecule
inhibitors of LSD1