Assays to Study Hypoxia-Inducible Factor Prolyl Hydroxylase Domain 2 (PHD2), a Key Human Oxygen Sensing Protein.

Molecular oxygen is essential for all multicellular life forms. In humans, the hypoxia-inducible factor (HIF) prolyl hydroxylase domain-containing enzymes (PHDs) serve as important oxygen sensors by regulating the activity of HIF, the master regulator that mediates cellular oxygen homeostasis, in an oxygen-dependent manner. In normoxia, PHDs catalyze the prolyl hydroxylation of HIF, which leads to its degradation and prevents cellular hypoxic response to be triggered.

Incorporation of SARS-CoV-2 spike NTD to RBD protein vaccine improves immunity against viral variants.

Emerging SARS-CoV-2 variants pose a threat to human health worldwide. SARS-CoV-2 receptor binding domain (RBD)-based vaccines are suitable candidates for booster vaccines, eliciting a focused antibody response enriched for virus neutralizing activity. Although RBD proteins are manufactured easily, and have excellent stability and safety properties, they are poorly immunogenic compared to the full-length spike protein.

Carbon Monoxide is an Inhibitor of HIF Prolyl Hydroxylase Domain 2.

Hypoxia-inducible factor prolyl hydroxylase domain 2 (PHD2) is an important oxygen sensor in animals. By using the CO-releasing molecule-2 (CORM-2) as an in situ CO donor, we demonstrate that CO is an inhibitor of PHD2. This report provides further evidence about the emerging role of CO in oxygen sensing and homeostasis.

An investigation into the effect of ribosomal protein S15 phosphorylation on its intermolecular interactions by using phosphomimetic mutant.

An investigation using recombinant ribosomal proteins and synthetic peptide models was conducted to uncover the effect of the introduction of a negative charge at the C-terminal tail of ribosomal protein S15. Our results help provide a chemical rationale towards understanding how G2019S LRRK2, a common clinical mutation, causes Parkinson's disease.

Small-molecule screening yields a compound that inhibits the cancer-associated transcription factor Hes1 via the PHB2 chaperone.

The transcription factor Hes family basic helix-loop-helix transcription factor 1 (Hes1) is a downstream effector of Notch signaling and plays a crucial role in orchestrating developmental processes during the embryonic stage. However, its aberrant signaling in adulthood is linked to the pathogenesis of cancer. In the present study, we report the discovery of small organic molecules (JI051 and JI130) that impair the ability of Hes1 to repress transcription.

NMR studies of the non-haem Fe(II) and 2-oxoglutarate-dependent oxygenases.

The non-haem Fe(II) and 2-oxoglutarate (2OG)-dependent oxygenases belong to a superfamily of structurally-related enzymes that play important biological roles in plants, microorganisms and animals. Structural, mechanistic and functional studies of 2OG oxygenases require efficient and effective biophysical tools. Nuclear magnetic resonance (NMR) spectroscopy is a useful tool to study this enzyme superfamily.