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Biomedical subjects

R S Morgan

Publications and source records attributed to R S Morgan.

At least 19 recordsLinked to original sources

A new classification of the amino acid side chains based on doublet acceptor energy levels.

We describe a new classification of the amino acid side chains based on the potential energy level at which each will accept an extra (doublet) electron. The doublet acceptor energy level, and the doublet acceptor orbital were calculated using semiempirical INDO/2-UHF molecular orbital theory. The results of these calculations show that the side chains fall into four groups. We have termed these groups repulsive, insulating, semiconducting, and attractive in accordance with where each lies on the relative energy scale. We use this classification to examine the role of residues between the donor and acceptor in modulating the rate and mechanism of electron transfer in proteins. With the calculated acceptor levels, we construct a potential barrier for those residues between the donor and acceptor. It is the area beneath this barrier that determines the decay of electronic coupling between donor and acceptor, and thus the transfer rate. We have used this schematic approach to characterize the four electron transfer pathways in myoglobin recently studied by Mayo et al. (Mayo, S.L., W.R. Ellis, R.J. Crutchley, and H.B. Gray. 1986. Science [Wash. DC]. 233:948-952).

Amino Acids

A new method for computing the macromolecular electric potential.

A general methodology is developed for the rigorous computation of the electrostatic potential for a protein of arbitrary shape, assuming the presence of linear dielectric media. The theory proceeds by considering the distribution of induced polarization charge at the dielectric interface, rather than by attempting a direct solution of Poisson's equation (as in the finite-difference approach of Warwicker & Watson). The method is applied to a study of two-dimensional model proteins, where it is shown that the presence of a cleft is associated with a region of relatively high potential in the solvent medium. The results of a preliminary calculation in three dimensions for the protein lysozyme are also discussed; again, a region of enhanced potential is observed near the cleft at the active site. Our computational evidence supports the suggestion of Warwicker & Watson that clefts are associated with important electrostatic effects.

Electricity

Chains of alternating sulfur and pi-bonded atoms in eight small proteins.

This paper demonstrates the existence of regions in eight small globular proteins in which the side chains of sulfur-containing amino acids (cysteine and methionine) alternate in space with side chains of aromatic amino acids (histidine, phenylalanine, tryptophan and tyrosine). The proteins are: rubredoxin, high potential iron protein, cytochrome c, flavodoxin, deoxyhemoglobin, trypsin inhibitor, ribonuclease-S, and lysozyme. The sulfur-pi-bonded 'chains' involve a minimum of five and a maximum of 10 amino acids, and contain the most polarizable atoms within proteins. S-pi-chains give extra stability to the folding of proteins; they may also afford paths for the step-wise movement of electrons.

Amino Acid Sequence

Permeability in atherosclerosis: fluorescence test in green light with trypan blue.

A new microscopic fluorescence method for trypan blue at 570 nm has been used to follow the entry of albumin into the atheromatous rabbit aorta. Permeability into the inner aortic wall increases before the onset of gross lesions and seems just to precede intraendothelial deposition of lipid. Thereafter, permeability of the inner wall progressively increases until streaks or small plaques develop. These raised lesions stain and fluoresce variably, some intensely so while others are almost unreactive. This variability might reflect the difference between progressive and quiescent lesions. However, a zone of increased permeability surrounds many raised lesions, suggesting that the edge is a major site of growth and progression.

Animals

Regression of atheroma in the rabbit.

Ten studies in the literature concerning regression of rabbit atheroma were re-examined. In studies where cholesterol content was referred to weight, a degree of regression was noted in 3/4 studies. Such regression might at least partly have resulted from the dilution effect of the atheroma contents when results were expressed on a weight basis. By contrast, when results were referred to length or protein, partial regression was seen in only 1/4 studies. Mild atheroma induced by short-term cholesterol feeding did seem to regress in 2/2 studies.

Animals

Dietary restriction and regression of atherosclerosis.

Rabbits were fed a cholesterol-enriched diet to render them atheromatous. After 3 months on this diet they were switched to a low-lipid stock diet. Some animals were killed at this point, while the rest were divided into (a) a group allowed to eat ad-libitum and (b) a resticted group allowed to eat half by weight of what the ad-libitum group consumed. Most animals were killed at 9 months (i.e. after 6 months' regression). The group allowed the restricted diet showed a 27% weight loss, but their serum cholesterol fell slightly more slowly than that of the ad-libitum animals. Likewise, atherosclerosis was slightly worse in the restricted than in the ad-libitum group. The results do not support the view that severe dietary restriction causes atherosclerosis to regress.

Animals

Frequency-dependent diffraction from enzymatic breathing modes.

The intensity of the time-dependent Fourier transform of any macro-molecule which contains a cleft of the sort that exists in the protein lysozyme is derived. It is shown that there is a region of this transform in which this intensity varies nearly sinusoidally with time with a frequency equal to that of the macromolecule's breathing mode of vibration, and where, therefore, the diffracted power will be primarily at this single frequency. Observation of this power will allow the experimental determination of the frequency of this mode, which is expected to be much lower than those observable by Raman spectroscopy.

Chemical Phenomena

Zinc in Entamoeba invadens.

Atomic absorption spectroscopy, electron microprobe analysis, and dithizone staining of trophozoites and cysts of Entamoeba invadens demonstrate that these cells have a high concentration of zinc (approximately 10(-6) microgram per cell or 1 percent of their dry weight). In the cysts of this organism, the zinc is confined to the chromatoid bodies, which previous work has shown to contain crystals of ribosomes. The chemical state and function of this zinc are unknown.

Chromatids

Zinc in sephadex.

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Dextrans