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.

Solution structure of linear battacin lipopeptides - the effect of lengthening fatty acid chain.

In recent years, lipopeptides have received attention for their enhanced antimicrobial activity, especially against multi-drug resistant (MDR) pathogens. We have previously reported that the bacterial soil extracted, novel cyclic lipopeptide, battacin, and its synthetic analogues have enhanced antimicrobial activity against various Gram negative, Gram positive and fungal pathogens. In particular, the modification of the hydrophobic fatty acid chain and molecular structure has improved its activity. We have used small angle X-ray scattering (SAXS) and circular dichroism (CD) to characterise the low resolution structure of battacin lipopeptides containing covalently bonded fatty acid chains and the one without it. In the absence of fatty acids or with short fatty acid chain, the peptides adopted an extended random coil structure that is best described barbell-like shape, while fatty acids that are sufficiently long induced an aggregation into a ∼4.0 nm diameter core shell sphere. While the kinked structure found within this barbell shape may have a role in antimicrobial activities, the self-assembly of the battacin analogue with the longest fatty acid chain may have a correlation to the declined antibacterial activities.

An improved method for the heterologous production of soluble human ribosomal proteins in Escherichia coli.

Human ribosomal proteins play important structural and functional roles in the ribosome and in protein synthesis. An efficient method to recombinantly produce and purify these proteins would enable their full characterisation. However, the production of human ribosomal proteins can be challenging. The only published method about the recombinant production of human ribosomal proteins involved the recovery of proteins from inclusion bodies, a process that is tedious and may lead to significant loss of yield. Herein, we explored the use of different Escherichia coli competent cells and fusion protein tags for the recombinant production of human ribosomal proteins. We found that, by using thioredoxin as a fusion protein, soluble ribosomal protein could be obtained directly from cell lysates, thus leading to an improved method to recombinantly produce these proteins.

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. It has been applied to obtain information about enzyme kinetics, identify and characterise 2OG oxygenase-catalysed oxidation products, elucidate the catalytic mechanism, monitor ligand binding and study protein dynamics. This review summarises the types of information that NMR spectroscopy can provide in the studies of 2OG oxygenases, highlights the advantages of the technique and describes its drawbacks.