Ab initio study of aspartic and glutamic acid: supplementary evidence for structural requirements at position 9 for glucagon activity

Abstract Our previous work established that position 9 aspartic acid in glucagon was a critical residue for transduction of the hormone response. An uncoupling of the binding interaction from adenylate cyclase activation was demonstrated by the observation that amino acid replacements at position 9 resulted in peptides that had no measurable adenylate cyclase activity yet were still recognized by the glucagon receptor. It was also later shown that His' played a major role in activation, and it was suggested that an electrostatic interaction between the aspartic acid carboxylate and the histidine imidazole occurred as part of the activation mechanism. This did not preclude intermolecular interactions of this aspartic acid with other residues within the receptor binding site. The observation that a conservative substitution of glutamic acid for aspartic acid at position 9 was sufficient to result in the potent antagonist, des-His'd[Glu']glucagon amide, implied that even glutamic acid possessed the minimum properties necessary for inhibition, and that the precise position of the carboxyl group at position 9 in glucagon was an absolute requirement for full agonist activity. The present investigation was conducted with ab initio calculations and molecular modeling to shed some light on the source of this phenomenon

Observations of trace gases and aerosols over the Indian Ocean during the monsoon transition period

Characteristics of trace gases (O3, CO, CO2, CH4 and N2O) and aerosols (particle size of 2.5 micron) were studied over the Arabian Sea, equatorial Indian Ocean and southwest part of the Bay of Bengal during the monsoon transition period (October-November, 2004). Flow of pollutants is expected from south and southeast Asia during the monsoonal transition period due to the patterns of wind flow which are different from the monsoon period. This is the first detailed report on aerosols and trace gases during the sampled period as the earlier Bay of Bengal Experiment (BOBMEX), Arabian Sea Monsoon Experiment (ARMEX) and Indian Ocean Experiments (INDOEX) were during monsoon seasons. The significant observations during the transition period include: (i) low ozone concentration of the order of 5 ppbv around the equator, (ii) high concentrations of CO2, CH4 and N2O and (iii) variations in PM2.5 of 5-20μg/m3