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Biomedical subjects

J Janin

Publications and source records attributed to J Janin.

At least 127 records · Page 7Linked to original sources

The accessible surface area and stability of oligomeric proteins.

Protein structures are stabilized by hydrophobic and van der Waals forces, and by hydrogen bonds. The relation between these thermodynamic quantities and the actual three-dimensional structure of proteins can not be calculated precisely. However, certain empirical relations have been discovered. Hydrophobic energy is gained by the reduction of surface in contact with water. For monomeric proteins, the area of the surface accessible to solvent, and of that buried in the interior, is a simple function of molecular weight. Proteins with different shapes and secondary structures, but of the same molecular weight, have the same accessible surface area. It has been argued that there is no similar relationship for large oligomeric proteins. In this paper we show that the surface areas of oligomeric proteins, and the areas of the surface buried within them, are directly related to relative molecular mass. Although oligomers of the same molecular weight bury the same amounts of surface, the proportions buried within and between subunits vary. This has important implications for the role of subunit interfaces in the stability and activity of oligomeric proteins.

Chemical Phenomena↗

Phosphorylation of anti-HIV nucleoside analogs by nucleoside diphosphate kinase.

The reaction of NDP kinase with antiviral nucleoside triphosphates used in antiviral therapies was studied at the presteady state by fluorescence stopped-flow and compared with the steady-state parameters. The affinity of the analogs was determined by fluorescence titration of a mutated enzyme with an inserted Trp in the binding site. The lack of the 3' hydroxyl in analogs is shown to decrease the kcat more than the KD.

Anti-HIV Agents↗

Activation of anti-reverse transcriptase nucleotide analogs by nucleoside diphosphate kinase: improvement by alpha-boranophosphate substitution.

Nucleoside activation by nucleoside diphosphate kinase and inhibition of HIV-1 reverse transcriptase were studied comparatively for a new class of nucleoside analogs with a borano (BH3-) or a thio (SH) group on the alpha-phosphate. Both the alpha-Rp-borano derivatives of AZT and d4T improved phosphorylation by NDP kinase, inhibition of reverse transcription as well as stability of alpha-borano nonophosphate derivatives in terminated viral DNA chain.

Anti-HIV Agents↗