A continuum model to study the internal fluctuations in globular proteins

The salient features of the differential equation model to study protein dynamics are presented with results for 19 proteins.     

Tracing paternal ancestry in mice, using the Y-linked, sex-determining locus, Sry

The molecular evolution of mammalian Y-linked DNA sequences is of special interest because of their unique mode of inheritance: most Y- linked sequences are clonally inherited from father to son. Here we investigate the use of Y-linked sequences for phylogenetic inference. We describe a comparative analysis of a 515-bp region from the male sex- determining locus, Sry, in 22 murine rodents (subfamily Murinae, family Muridae), including representatives from nine species of Mus, and from two additional murine genera--Mastomys and Hylomyscus. Percent sequence divergence was < 0.01% for comparisons between populations within a species and was 0.19%-8.16% for comparisons between species. Our phylogenetic analysis of 12 murine taxa resulted in a single most- parsimonius tree that is highly concordant with phylogenies based on mitochondrial DNA and allozymes. A total evidence tree based on the combined data from Sry, mitochondrial DNA, and allozymes supports (1) the monophyly of the subgenus Mus, (2) its division into a Palearctic group (M. musculus, M. domesticus, M. spicilegus, M. Macedonicus, and M. spretus) and an Oriental group (M. cookii++, M. cervicolor, and M. caroli), and (3) sister-group relationships between M. spicilegus and M. macedonicus and between M. cookii and M. cervicolor. We argue that Y- chromosome DNA sequences represent a valuable new source of characters for phylogenetic inference.      

Active and passive cation transport and L antigen hertogeneity in low potassium sheep red cells

Several lines of experimental evidence are presented suggesting that the L antigens in low potassium (LK) sheep red cells are associated with separate Na(+)K(+) pump flux is distinct from the action of anti-L(l) on K(+) leak flux, implying that K(+) leak transport sites may not be converted into active pumps by the L antiserum. Treatment of LK red cells with trypsin completely abolished both the stimulation of K(+) pump flux and the enhancement of the rate of ouabain binding brought about by anti- L. That this effect is due to a total destruction of the L(p) determinant associated with the LK pump was evident from the complete failure of anti-L(p) to bind to trypsinized LK red cells. The L(p) antigen can be effectively protected against the trypsin attack by prior incubation with anti-L, indicating that the sites for antibody binding and trypsin action may be closely adjacent at the structural level. Trypsin treatment, however, did not interfere with anti-L(l) reducing ouabain insensitive K(+) leak influx, nor did it prevent binding of anti-L(ly), the hemolytically active L antibody which is probably identical with anti-L(l). The functional independence of the L(p) and L(l) sites was documented by the observation that anti-L(l) still reduced K(+) leak influx in LK cells with experimentally induced high potassium concentrations, at which K(+) pump flux is fully suppressed, whether or not anti-L(p) was binding to the L(p) antigen associated with the LK pump.     

A study of the preferred environment of amino acid residues in globular proteins

In the native folded conformation of a globular protein, amino acid residues distant along the polypeptide chain come together to form the compact structure. This spatial structure is such that most of the polar residues are on the surface and have contact with the solvent medium and the nonpolar residues buried in the interior which have contact with similar nonpolar side chains. This cooperativity and mutual interaction among the randomly aligned amino acid residues suggest that each type of residue may prefer to have a specific environment. To gain more insight into this aspect of residue-residue cooperativity, a detailed analysis of the preferred environment associated with each of the 20 different amino acid residues in a number of protein crystals has been carried out. The variation of nonpolar nature computed for different sizes of spheres shows that the spatial region between radii of 6 and 8 Å is more favored for hydrophobic interactions and indicates that the influence of each residue over the surrounding medium extends predominantly up to a distance of 8 Å. The analysis of the surrounding amino acid residues associated with each type of residue shows that there is a definite tendency for each type of residue to have association with specific residues. The variation in environment is found even within the polar group as well as in the nonpolar group of residues. The surrounding residues associated with isoleucine, leucine, and valine are purely nonpolar. Proline, a nonpolar residue, is often surrounded by polar residues. The surrounding nonpolar nature of the tryptophan and tyrosine residues implies that even a single polar atom in a nonpolar side chain is sufficient to reduce their hydrophobic environment. There exists a high degree of mutual residue-residue cooperativity between the pairs glutamic acid-lysine, methionine-arginine, asparagine-tryptophan, and glutamine-proline, and the mutual residue-residue noncooperativity is high for the pairs methionine-aspartic acid, cysteine-glutamic acid, histidine-glutamine, and leucine-asparagine. The formation of secondary and tertiary structures is discussed in terms of the preferred environment and mutual cooperativity among various types of amino acid residues.     

Conformational Characteristics of Mixed Sugar Puckered Deoxydinucleoside Triphosphate Units d-pCpGp and d-pGpCp from Energy Minimization Studies

Abstract

The deoxydinucleoside triphosphate units d-pCpGp and d-pGpCp were subjected to a rigorous theoretical investigation with a view to describing their distinctive conformational characteristics. For each unit 216 probable three-dimensional forms defined by the backbone-base dihedral angles and sugar pucker modes were considered for conformational energy minimization process and scrutinized with reference to properties, such as base-stacking, hydrogen-bonding, internal flexibility and base sequence-phosphate influence. The P-O bond torsions and the phosphate groups were treated with special attention. The results reveal a number of preferred conformational states other than the known helical forms, such as, A-, B-, C-, Z-, and Watson-Crick conformation. Many interesting one-step (change in only one of the dihedral angles or sugar puckers) conformational transitions which involve just about a kcal/mol of energy came to light. The two base sequences CG and GC were noted to differ strikingly in many of their conformational characteristics.     

Impacts of cage culture on physico-chemical and bacteriological water quality in Lake Volta,Ghana

The effects of cage fish farming on physico-chemical and bacteriological water quality in Lake Volta, Ghana, were investigated in 2013–2014. Farmed and unfarmed (control) areas of the lake were selected for monitoring. Nutrients, temperature, dissolved oxygen, conductivity, turbidity, pH, total coliforms, Pseudomonas and Vibrio spp. in the water were monitored monthly. Analyses of the water samples were carried out according to standard procedures. Physico-chemical quality of the water in both farm and control sites were within ranges typical of minimally impacted water and did not vary significantly between the two contrasting sites. The bacteriological analysis, however, revealed contamination of the lake water by fish farming. The bacterial counts at the farmed sites were significantly higher (p < 0.05) than those of the control sites, with figures at the farmed sites ranging from 132 to 1 708 cfu 100 ml?1 for total coliforms, 514 to 5 170 cfu 100 ml?1 Pseudomonas spp. and 14 to 516 cfu 100 ml?1 for Vibrio spp. The results suggested that cage fish farming has increased bacterial loads in the lake water, but has had minimal impact on its physico-chemical quality.     

A study of aromatic hydrogen bonds of peptides with aromatic amino acid side-chains

The importance of hydrogen bonding studies lies in their structural, biological and medicinal applications. Non-conventional hydrogen bonds are weak, but are found to play an important role in biological molecules. In view of their importance,a study of the aromatic hydrogen bonds in peptides with aromatic amino acid side chains was carried out. The results indicate a reasonable probability for their occurrence, thereby enumerating their distinct features.     

Design, synthesis and anti-microbial activity of 1H-pyrazole carboxylates

In a SAR study, we have synthesized a few 1H-pyrazole carboxylate related microbicides using Vilsmeier reagent. The anti-microbial screening results of 1H-pyrazole-3-carboxylate are reported here for the first time. The effect of 1H-pyrazole carboxylates on the mycelial growth of plant pathogenic fungi is revealed. The first X-ray structure in the family of microbicidal 1H-pyrazole-4-carboxylates is presented.     

Structural studies on a low oxygen affinity hemoglobin from mammalian species: Sheep (Ovis aries)

Hemoglobin (Hb) is in equilibrium between low affinity Tense (T) and high affinity Relaxed (R) states associated with its unliganded and liganded forms, respectively. Mammalian species can be classified into two groups on the basis of whether they express ‘high’ and ‘low’ oxygen affinity Hbs. Although Hbs from former group have been studied extensively, a limited number of structural studies have been performed for the low oxygen affinity Hbs. Here, the crystal structure of low oxygen affinity sheep methemoglobin (metHb) has been determined to 2.7 Å resolution. Even though sheep metHb adopts classical R state like quaternary structure, it shows localized quaternary and tertiary structural differences compared with other liganded Hb. The critical group of residues in the “joint region”, shown as a major source of quaternary constraint on deoxyHb, formed unique interactions in the α1β2/α2β1 interfaces of sheep metHb structure. In addition, the constrained β subunits heme environment and the contraction of N-termini and A-helices of β subunits towards the molecular dyad are observed for sheep metHb structure. These observations provide the structural basis for a low oxygen affinity and blunt response to allosteric effector of sheep Hb.