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Biomedical subjects

R Parthasarathy

Publications and source records attributed to R Parthasarathy.

At least 91 records · Page 5Linked to original sources
PubMed1985

Intercalation of water molecules between nucleic acid bases in the crystal structures of 6-azathymine hemihydrate and 5-amino-2-thiocytosine dihydrochloride dihydrate.

The crystal structure of 6-azathymine hemihydrate (6AzTH) exhibits a novel intercalation of water molecules interposed half-way between the modified bases 6.3 to 6.7 A apart. The crystal contains four molecules of 6-azathymine (6AzT) and two water molecules as the independent repeating unit. These two water molecules together with the four bases form two separate water sandwiches. In the crystal structure these sandwiches form two sets of local clusters. The anhydrous crystalline form of 6AzT, on the other hand, is stabilized by base stacking interactions. Both the water molecules in 6AzTH that are involved in sandwich formation have trigonal coordination around them. A reexamination of the crystal structure of 5-amino-2-thiocytosine (5A2TC) revealed that one of the water molecules in this structure also forms a water sandwich and has trigonal coordination whereas the other water molecule with tetrahedral coordination does not form a sandwich. The environment and the characteristics of the intercalated water molecule in these structures suggest a possible role for such water intercalations in the dynamics of DNA. Crystals of 6AzTH are monoclinic, space group P21/n, with unit cell parameters a = 8.861 (1), b = 13.177 (3), c = 20.662 (2) A, beta = 93.35 (1) degrees, and Z = 16. From diffractometer data (2503 reflections, greater than or equal to 3 sigma), the crystal structure was solved and refined to an R of 0.056.

Base Sequence↗
PubMed1984

Conformational variability of NAD+ in the free and bound states: a nicotinamide sandwich in NAD+ crystals.

X-ray analysis of the free-acid crystal form of the coenzyme nicotinamide adenine dinucleotide (NAD+) revealed a conformational difference between the free NAD+ molecule and one bound in enzymes or complexed to Li+ ions. The pyrophosphate group showed asymmetry in the phosphate-oxygen bonds of the phosphate-oxygen-phosphate link; this bond at the nicotinamide side of the link is longer than that at the adenosine side by 0.04 angstrom. The crystal structure showed a novel intermolecular stacking of adenine and water molecules on opposite sides of nicotinamide that gives rise to a nicotinamide sandwich.

Alcohol Dehydrogenase↗
PubMed1984

Lack of relationship between hepatic toxicity and acetylator phenotype in three thousand South Indian patients during treatment with isoniazid for tuberculosis.

The results are presented of a retrospective analysis of the incidence of jaundice among 3,000 patients with pulmonary tuberculosis and of the activities of serum aspartate aminotransferase among 850 according to their isoniazid acetylator phenotype. The patients had been treated with a variety of isoniazid-containing regimens in a series of controlled clinical trials in South India. The results show that rapid acetylators are no more prone to develop isoniazid-induced hepatic toxicity than are slow acetylators.

Acetylation↗
PubMed1984

Anxiety provoking situations in Indian families.

Life situations pertaining to the relationship dimension are viewed in respect of families of anxiety patients and normals. Grand-parents' interference, parents-in-law relationships, parents' role functioning, siblings' interaction, marital relationships and other relatives' cooperation are studied for 20 anxiety patients and 40 normals based on group matching. It was found that frequent interference of grand-parents, dissatisfaction with parents-in-law, inadequate mutually contradictory parents' role functioning, disharmonious siblings interaction, threatening and conflicting marital life and lack of cooperation and support on the part of other relatives seem to be sources of anxiety in the Indian setting.

Anxiety Disorders↗
PubMed1984

Conformation and hydrogen bonding of N-formylmethionyl peptides. Parallel beta-sheet in the crystal structure of N-formyl-L-methionyl-L-valine.

Crystals of N-formyl-L-methionyl-L-valine (C11H20N2O)4S, M.W. = 276.3) are orthorhombic, space group )2(1)2(1)2(1) with cell constants at 294K of a = 4.851 (1), b = 14.925 (1), c = 19.745 (3) A, V = 1429.8 (1) A3, Z = 4 and observed (Dm) and calculated (Dx) of 1.49 and 1.488 g x cm-3, respectively. The crystal structure was solved using automatic diffractometer data (1260 reflections larger than or equal to 3 sigma) and refined to a final R-value of 0.035. This structure contains a short (2.626 (3) A) intermolecular hydrogen bond between the carboxyl OH and the N-acyl oxygen, a feature common to most N-acylamino acids and N-acylpeptides. The peptide is nearly planar (omega = 174.6 (5)); the values of psi 1, phi 2, psi 1T and psi 2T are, respectively, 131.8 (4) degrees, -139.9 (5) degrees, -39.3 (4) degrees and 142.1 (4) degrees. The methionine side chain is not zig-zag transplanar; the side chain torsion angles are: chi 1(1) = -60.0 (4) degrees, chi 2(1) = 176.0 (4) degrees and chi 3(1) = 71.8 (4) degrees. The two C gamma's for valine have psi 1-values of -64.4 (5) degrees and 173.7 (5) degrees. The formation of the parallel rather than antiparallel beta-sheet structure, the participation of the N-formyl group in the parallel beta-sheet and the use of C-H ... O hydrogen bonds to stabilize the beta-sheet are novel features found in this structure.

Chemotactic Factors↗
PubMed1983

Lipids and cholesterol esterifying enzyme changes by Anna Pavala Sindhooram therapy in experimental rat hyperlipaemia.

The effect of Anna Pavala Sindhooram (APS), an indigenous drug showing lipid lowering action was tested in experimental rat atherosclerosis induced by feeding an atherogenic diet. APS was found to decrease the levels of serum cholesterol and phospholipids while triglycerides remained unaffected in atherogenic diet fed rats. Lipid levels in the aorta, liver and intestine were also increased by atherogenic diet feeding, and APS administration with diet restriction reversed this trend. Cholesterol ester was lowered. Both cholesteryl ester hydrolase (CEH) and synthetase (CES) activities in the tissues were elevated while the CEH/CES ratio was lowered in atherosclerosis. APS administration led to a decrease in enzyme activities and an increase in the CEH/CES ratio. APS in vitro inhibited both enzyme activities. NMR spectroscopic studies showed that the soluble components of APS bind or modify cholesterol. Iron, copper, magnesium and calcium present in APS may play a role in the removal of cholesterol ester from the aorta and its disposal.

Animals↗
PubMed1983

Classes of unitarizable derived functor modules.

For a real semisimple Lie group G, the description of the unitary dual remains an elusive question. One of the difficulties has been the lack of technique for constructing unitary representations. Unitary induction from parabolic subgroups of G yields unitary representations by the very definition of these representations. However, not all unitary irreducible representations of G are obtained by this type of induction. In addition, we need derived functor parabolic induction [ef. Vogan, D. (1981) Representations of Real Reductive Lie Groups (Birkhäuser, Boston)] to describe all irreducible representations of G. For this second type of induction, the obvious analogues from parabolic subgroup induction regarding unitarity are false. In this announcement, we describe a setting where derived functor parabolic induction yields unitary representations of G. These results include proofs of unitarity for some of the representations conjectured to be unitary by Vogan and Zuckerman [(1983) Invent. Math., in press] and also proofs of unitarity for some which lie outside the domain described in those conjectures.

Journal Article↗
PubMed1982

X-ray structure of a dinucleoside monophosphate A2'p5'C that contains a 2'-5' link found in (2'-5')oligo(A)s induced by interferons: single-stranded helical conformation of 2'-5'-linked oligonucleotides.

In order to understand why DNA and RNA have the 3'-5' and not the 2'-5' link and to delineate the stereochemistry of the 2'-5' phosphodiester links, we crystallized and carried out a very accurate x-ray diffraction analysis of A2 p5'C, an analog of A2' p5'A. Contrary to numerous reports in the literature that conclude that the tendency for 2'-5' nucleotides to stack intramolecularly is stronger than for 3'-5' counterparts, we find hardly any intramolecular base stacking for this molecule but find an intramolecular "stacking" of the ribose oxygen-4' of cytidine on top of the adenine ring. Although A2' p5'C shows the standard conformational features usually found for 3'-5' nucleotides, the overall stereochemistry of 2'-5' nucleotides is quite different because the 2' link orients the backbone inwards to the bases unlike the 3' and 5' links that orient it away from the bases. With the conformational features found for A2' p5'C, it is possible to build a very compact right-handed single-stranded helix but not a double helix. Such a preference for single-stranded helices may be the reason for the absence of 2'-5' bonds in DNA and RNA even though the 2'-5' bonds are formed more readily then 3'-5' bonds.

Adenine Nucleotides↗
PubMed1982

New patterns of hydrogen bonded interactions between polypeptide chains. Crystal and molecular structure of glycylglycylglycine.

Crystals of glycylglycylglycine (C6H-11N3O4), grown from an aqueous methanol solution, are triclinic, space group P1, with the unit cell dimensions (at 22 +/- 3 degrees) a = 11.656(3), b = 14.817(3), c = 4.823(2) A, alpha = 88.45(3), beta = 95.96(3), gamma = 105.42(3) degrees, Z = 4 (with two molecules in the asymmetric unit) with a density of Dobs = 1.58 g X cm -3 and Dcalc = 1.572 g X cm -3. The crystal structure was solved by a combination of multisolution and trial and error methods and refined with full-matrix least-squares method to a final R value of 0.036 for the observed 3021 reflections (I greater than or equal to 2 sigma). The conformation of the two molecules I and II in the asymmetric unit is very similar (except around the N-terminal end); they have the fully extended trans-planar conformation, and have omega values ranging from 2 to 4 degrees. The peptide chain repeating distances (C1 alpha - C3 alpha) are 7.27 A and 7.18 A in the two molecules as compared with the value of 6.68 A for extended beta-sheets with beta-carbons. There are four different interactions between these two molecules characterized by different hydrogen bonding. Molecule I is hydrogen bonded to a neighboring molecule I using four hydrogen bonds. Molecule II is hydrogen bonded to another II, using bifurcated interactions involving the peptide nitrogen. Molecule I is hydrogen bonded to two different molecules II forming distinctly different hydrogen bonding patterns from the two mentioned above. The molecules are packed in rows, in a head-to-tail fashion (C-terminal opposite N-terminal) and are held together in sheets by hydrogen bonds between carbonyl and amide groups, corresponding to the very familiar anti-parallel pleated sheet arrangement for polypeptides. The hydrogen bonds involving the amino nitrogens as donors are significantly longer and presumably weaker compared to those involving the NH+3 group. The C=O distances show variations that correlated with hydrogen bonding. The N-H...O angle varies from 152 to 174 degrees and the bent N-H...O hydrogen bonds show bifurcated interactions.

Crystallography↗
PubMed1980

Carboxybiotin translocation mechanisms suggested by diffraction studies of biotin and its vitamers.

Biotin is a coenzyme that fixes CO2 for transfer in a family of carboxylase, decarboxylase, and transcarboxylase enzymes. Their enzyme reactions involve two basic steps during which a carboxybiotinyl intermediate forms at one site and translocates to a second (distinct) site for CO2 transfer. Our diffraction studies of biotin and its vitamers suggest that translocation involves rotation about one, or at most two, bonds in biotin's valeryl chain. The rotations are energetically economical gauche in equilibrium trans rotations about the two valeryl bonds nearest the biotin bicyclic ring. They move a carbon atom of a CO2 moiety bound at N-1' approximately 7 A, a distance in accord with spectroscopic measurements of one of the biotin enzymes. From our studies we infer that sulfur in biotin imparts to the valeryl chain a conformational variability necessary for bond rotation and, hence, translocation between catalytic sites.

Biotin↗
PubMed1978

Conformation of L-cystathionine, a carba analog of cystine, and stereochemistry of hormone-receptor interactions.

The conformation of L-cystathionine, a carba analog of L-cystine, has been studied in the solid state using X-ray diffraction techniques. Crystal of L-cystathionine are tetragonal, space group P41 with cell constants a = 6.691(1) A, c = 21.998(3) A and Z = 4. From diffractometer data to the limit of 2theta = 162 degrees for Cukalpha, the structure was refined using full-matrix least-squares to an R value of 0.061. L-Cystathionine is isostructural chemically to L-cystine and its crystal structure is isomorphous to tetragonal L-cystine (Chaney, M.O. and Steinrauf, L.K. (1974) Acta Crystallogr. 1330, 711--716). The crystal structure of L-cystathionine is disordered, leading to two slightly differing conformers of L-cystathionine (each with half occupancy) with same helical sense but running in opposite directions and occupying the locations of L-cystine molecules in tetragonal L-cystine structure. Their conformational similarity, even when no sterical constraints such as cyclization are present, offers an explanation of the activities of the carba analogs of neuro-hypophysial hormones in terms of the structural integrity of the disulfide-like bridges.

Cystathionine↗
PubMed1978

Specific configurations of hydrogen bonding. I. Hydrogen bonding and conformational preferences of N-acylamino-acids, peptides and derivatives.

From a reexamination of the X-ray studies of the crystal structures of 27 N-acylamino acids, peptides and their derivatives and 30 linear peptides, it is concluded that specific formation of short intermolecular hydrogen bonds (2,5 to 2.6 A) from the carboxyl OH to the N-acyl oxygen is an important feature for N-acylamino acids. For N-acyl-N-amides, the formation of hydrogen bonds 2.7 to 2.9A long between N(acyl-H...O(amide) is strongly preferred. The dihedral angle delta between the N-acyl and carboxyl groups or adjacent amide groups shows a preference for values near 20 degrees or 90 degrees for N-acylamino acids and 90 degrees for N-acyl-N-amides.

Amino Acids↗