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R Parthasarathy

Publications and source records attributed to R Parthasarathy.

At least 73 records · Page 4Linked to original sources
PubMed1989

Role of water molecules in the crystal structure of Gly-L-Ala-L-Phe: a possible sequence preference for nucleation of alpha-helix?

The synthetic peptide Gly-L-Ala-L-Phe (C14H19N3O4.2H2O; GAF) crystallizes in the monoclinic space group P2I1), with a = 5.879(1), b = 7.966(1), c = 17.754(2) A, beta = 95.14(2) degrees, Dx = 1.321 g cm-3, and Z = 2. The crystal structure was solved by direct methods using the program SHELXS-86 and refined to an R value of 0.031 for 1425 reflections (greater than 3 sigma). The tripeptide exists as a zwitterion in the crystal and assumes a near alpha-helical backbone conformation with the following torsion angles: psi 1 = -147.8 degrees; phi 2, psi 2 = -71.2 degrees, 33.4 degrees; phi 3, psi 3 = -78.3 degrees, -43.3 degrees. In this structure, one water molecule bridges the COO- and NH3+ terminii to complete a turn of an alpha-helix and another water molecule participates in head-to-tail intermolecular hydrogen bonding, so that the end result is a column of molecules that looks like an alpha-helix. Thus, the two water molecules of crystallization play a major role in stabilizing the near alpha-helical conformation of each tripeptide molecule and in elongating the helix throughout the crystal. An analysis of all protein sequences around regions containing a GAF fragment by Chou-Fasman's secondary structure prediction method showed that those regions are likely to assume an alpha-helical conformation with twice the probability they are likely to adopt a beta-sheet conformation. It is conceivable that a GAF fragment may be a good part of the nucleation site for forming alpha-helical fragments in a polypeptide, with the aqueous medium playing a crucial role in maintaining such transient species.

Amino Acid Sequence↗
PubMed1989

Crystal structure and conformation of L-pyroglutamyl-L-alanine.

Crystals of the dipeptide, pyroglutamyl-alanine (C8H12N2O4) grown from aqueous methanol are monoclinic, space group P2(1) with the following cell parameters: a = 4.863(2), b = 16.069(1), c = 6.534(2)A and beta = 109.9(2) degrees, V = 480.0A3, Mr = 200.2, Dc = 1.385 g cm-3, and Z = 2. The crystal structure was solved by the application of direct methods and refined to an R value of 0.044 for 699 reflections with I greater than 2 sigma. The amide of the pyroglutamyl side chain is cis, omega 1 = 2.6(7) degrees; the peptide unit is trans and appreciably non-planar (omega 2 = 167.4(5) degrees). The backbone torsional angles are: psi 1 = 166.1(5), phi 2 = -90.3(6), and psi 2 = -22.4(6) degrees. This structure contains a short (2.551(5)A) intermolecular hydrogen bond between the carboxyl OH and the N-acyl oxygen, a feature common to most acyl amino acids and acyl peptides.

Chemical Phenomena↗
PubMed1989

Crystal structure and conformation of glycyl-glycyl-sarcosine.

Crystals of the tripeptide, glycyl-glycyl-sarcosine (C7H13N3O4) from aqueous methanol are orthorhombic, space group Pbcn with cell parameters at 294 K of a = 8.279(1), b = 9.229(4), c = 24.447(5)A, V = 1868.0 A3, M.W. = 203.2, and Z = 8. The crystal structure was solved and refined using CAD-4 data (1171 reflections greater than or equal to 3 sigma) to a final R-value of 0.053. The first peptide linkage is trans and planar whereas the second peptide link between Gly and sarcosine is cis and appreciably non-planar (w = 7.4 degrees). The peptide backbone has an extended conformation at the N-terminal part but adopts a polyglycine-II type of conformation at the C-terminal part. The backbone torsion angles are: psi 1 = -173.9, w1 = -177.8, (phi 2, psi 2) = (-178.8, -170.8), w2 = 7.4, (phi 3, psi 3) = (-81.6, 165.6 degrees).

Crystallography↗
PubMed1989

Crystal structure of L-2-oxothiazolidine-4-carboxylic acid.

Crystals of the title compound, L-2-oxothiazolidine-4-carboxylic acid, OTC (C4H5NO3S), grown from an aqueous solution are orthorhombic, space group P2(1)2(1)2(1) with the following cell parameters at 22 +/- 3 degrees: a = 5.381(1), b = 5.961(1), c = 17.929(3)A, V = 575.1A(3), Mr = 146.2, Dc = 1.688 g.cm-3, mu = 43.9 cm-1 and Z = 4. The crystal structure was solved by the application of direct methods and refined to an R value of 0.032 for 596 reflections with I greater than 3 sigma(I). The thiazolidine ring adopts a "twist" conformation. This structure contains a short (2.619(3)A) intermolecular hydrogen bond between the carboxyl OH and the oxygen of the 2-oxo moiety, a feature common to most acyl amino acids and acyl peptides.

Crystallization↗
PubMed1989

Conformation and hydrogen bonding of N-formylmethionyl peptides. II. Crystal and molecular structure of N-formyl-L-methionyl-L-phenylalanine.

Crystals of N-formyl-L-methionyl-L-phenylalanine (C15H20N2O4S), grown from aqueous methanol solution are orthorhombic, space group, P2(1)2(1)2(1), with cell parameters at 294K of a = 4.900(2), b = 17.947(4), c = 18.726(4)A, V = 1646.8A3, M.W. = 324.4, Z = 4 and Dm = 1.308 g/cc, and as expected, all nearly identical to that of N-f-D-Met-D-Phe studied by Jeffs, Heald, Chodosh & Eggleston (Int. J. Peptide Protein Res. 24, 442-446, 1984). The crystal structure was solved and refined using CAD-4 data (1095 reflections greater than or equal to 3 sigma) to a final R value of 0.042. Molecules related by the alpha-translation form a parallel beta-sheet rather than anti-parallel sheet as stated in the earlier study of Jeffs et al. The formation of the parallel rather than the anti-parallel beta-sheet structure, the use of the C-H ...O hydrogen bonds to stabilize the beta-sheet and the very short O-H ...O hydrogen bond between the carboxyl OH and the N-acyl oxygen atom emerge as the main structural features of the chemotactic N-formyl methionyl peptides.

Chemotactic Factors↗
PubMed1988

Structure of adenosine-5'-mononicotinate (AMN) trihydrate: an analog of NAD for testing intramolecular stacking.

C16H16N6O5.3H2O, Mr = 426.4, monoclinic, P21, a = 9.535 (2), b = 13.932 (2), c = 7.138 (2) A, beta = 93.13 (2) degrees, V = 946.85 A3, Z = 2, Dx = 1.495 g cm-3, lambda (Cu K alpha) = 1.5418 A, mu = 9.93 cm-1, F(000) = 428, T = 294 K, R = 0.045 and wR = 0.059 for 1460 observed reflections [I greater than 3 sigma (I)]. The AMN molecules, unlike NAD or other model structures of NAD, are not charged and exhibit intra- as well as intermolecular stacking of pyridine ring over adenine ring. There is extensive hydrogen bonding in the crystal involving the pyridine and adenine rings and the three water molecules. Rather surprisingly, the ester carbonyl O atom is not involved in the hydrogen bonding.

Hydrogen Bonding↗
PubMed1988

Studies on modified nucleic acid bases: structure of 3-isobutyl-1-methylxanthine.

C10H14O2, M = 222.3, monoclinic, P2/c, alpha = 4.882 (3), b = 8.715 (1), c = 25.955 (3) A, beta = 92.28 (1) degree, V = 1103.4 (9) A, Z = 4, Dm = 1.34, Dx = 1.338 g cm 3, Cu K alpha, lamba = 1.5418 A, mu = 7.62 cm 1, F(000) = 472, T = 294 k, R = 0.058 for 984 reflections I greater than 3 sigma (1). The isobutyl chain is oriented almost perpendicular to the xanthine ring (C(2)-N(3)-C(31)-C(32) +/- 99.8 (4)degree]. The isobutyl chain torsion angles are N(3)-C(31)-C(32)-C(33) +/- 62.2 (4) and N(3)-C(31) C(32)-C(34) +/- 174.1 (3) degree. The structure forms self-paired dimers of xanthine bases with a pair of N-H...O and a pair of weaker C-H...N hydrogen bonds across centers of inversion. There is a partial stacking of the xanthine bases.

1-Methyl-3-isobutylxanthine↗
PubMed1988

Conformation and sandwiching of bases by azido groups in the crystal structure of 3'-azido-3'-deoxy-thymidine (AZT), an antiviral agent that inhibits HIV reverse transcriptase.

The crystal structure of 3'-azido-3'-deoxy-thymidine (AZT), an antiviral agent that inhibits HIV reverse transcriptase, has been determined from three-dimensional x-ray diffractometer data. The crystal structure contains two independent molecules of AZT forming a hydrogen bonded dimer but exhibiting different conformations. These conformations are different from those theoretically calculated by molecular mechanics methods. The azido groups associate with each other and interrupt the base stacking, forming a sandwich of two stacked bases. The close conformational similarity of AZT to thymidine explains why AZT is a good substrate for thymidine kinase. The selective inhibition of reverse transcriptase by AZT is not due to any conformational restrictions imposed by the azido group but likely due to their stereoelectronic properties.

Azides↗
PubMed1987

Crystal structure and conformation of polypeptides: L-leucylglycylglycylglycine.

Crystals of L-leucylglycylglycylglycine, LGGG (C12H22N4O5), grown from an ethanol-water solution, are orthorhombic, space groups P2(1)2(1)2(1), with unit cell dimensions (at 22 +/- 3 degrees) a = 9.337(1), b = 10.995(1), c = 15.235(1)A, v = 1563.4 A3, Z = 4 with a density of Dobs = 1.29 g.cm-3 and Dcalc = 1.279 g.cm-3. The crystal structure was solved by the application of direct methods and refined to an R value of 0.029 for 1018 reflections with I greater than or equal to 2 sigma. The molecule exists as a zwitterion in the crystal. The trans peptide backbone takes up a folded conformation at the middle glycylglycyl link accompanied by a significant nonplanarity up to delta omega of 8 degrees at the middle peptide and is relatively more extended at the two ends. The molecules are linked together intermolecularly in an infinite sequence of head to tail 1-4' hydrogen bonds, as is typical of charged peptides. It is interesting to note that while glycylglycylglycine takes up an extended beta-sheet conformation, addition of Leu to the N-terminal results in a bent conformation.

Crystallization↗
PubMed1986

Hepatic toxicity in South Indian patients during treatment of tuberculosis with short-course regimens containing isoniazid, rifampicin and pyrazinamide.

Results are presented of the incidence of hepatitis, nearly always with jaundice, among 1686 patients in clinical trials of the treatment of spinal tuberculosis, of tuberculosis meningitis and of pulmonary tuberculosis with short-course regimens containing rifampicin, isoniazid, streptomycin and pyrazinamide. The incidence was high in patients treated with daily regimens of isoniazid and rifampicin: 16-39% in children with tuberculous meningitis, 10% in patients with spinal tuberculosis (non-surgical cases), and 2-8% in those with pulmonary tuberculosis. Hepatitis, in those receiving rifampicin occurred more often in slow than in rapid acetylators of isoniazid, the proportions amongst those whose acetylator phenotype had been determined being 11% of 317 slow acetylators and 1% of 244 rapid acetylators. In children with tuberculous meningitis, the risk of hepatitis with isoniazid 20 mg/kg (39%) was higher than that with 12 mg/kg (16%), and appreciably lower in patients given rifampicin twice-weekly (5%) rather than daily (21%). There was no indication that pyrazinamide contributed to the hepatic toxicity.

Adolescent↗
PubMed1986

Conformation of O6-alkylguanosines: molecular mechanism of mutagenesis.

The O6-alkylation of guanine residues in DNA treated with alkylating agents induce mutations due to mis-pairing resulting from the deprotonation of N1. In addition to the deprotonation of N1, the conformation of the O6-alkyl group with respect to N7 of guanine is very important. Here, we present X-ray crystallographic evidence that shows that the methyl group in O6-methylguanosine has a preference for the distal conformation, blocking the Watson-Crick sites. This distal conformation persists in the solid state for several analogs of O6-alkylguanosine also. This preferred conformation agrees with the result that poly(O6-methyl GMP) does not form any stable complex with poly(U). However, the mispairing of O6-methylguanine with thymine and the resultant G----A transition is known from in vitro studies. The above two opposite results strongly indicate that the conformation of the O6-alkyl group and the base pairing properties of O6-alkylguanine at the monomer and polymer levels must be different from the situation when the modified base is embedded with a small frequency in a duplex. It is interesting to note that the sterical blocking of the Watson-Crick site at the monomer level and the altered base pairing properties when present as occasional bases in a duplex emerge as a common property for several mutagenic bases like O6-alkylguanines, O4-methyluracil and N4-hydroxycytosine.

Base Composition↗
PubMed1986

Structure and conformation of linear peptides. VIII. Structure of t-Boc-glycyl-L-phenylalanine.

The crystal structure of t-Boc-glycyl-L-phenylalanine (C14H22N2O5, molecular weight = 298) has been determined. Crystals are monoclinic, space group P2(1), with a = 7.599(1) A, b = 9.576(2), c = 12.841(2), beta = 97.21(1) degrees, Z = 2, Dm = 1.149, Dc = 1.168 g X cm-3. Trial structure was obtained by direct methods and refined to a final R-index of 0.064 for 1465 reflections with I greater than 1 sigma. The peptide unit is trans planar and is nearly perpendicular to the plane containing the urethane moiety. The plane of the carboxyl group makes a dihedral angle of 16.0 degrees with the peptide unit. The backbone torsion angles are omega 0 = -176.9 degrees, phi 1 = -88.0 degrees, psi 1 = -14.5 degrees, omega 1 = 176.4 degrees, phi 2 = -164.7 degrees and psi 2 = 170.3 degrees. The phenylalanine side chain conformation is represented by the torsion angles chi 1 = 52.0 degrees, chi 2 = 85.8 degrees.

Dipeptides↗
PubMed1986

Structure and conformation on linear peptides. VI. Structure of D,L-alanyl-L,D-norvaline.

The dipeptide, (DL)-alanyl-(DL)-norvaline, crystallizes in the monoclinic space group P2(1)/c, with a = 12.559(2)A, b = 5.265(1), c = 16.003(3), beta = 103.53(2) degrees, Z = 4. The structure was solved by direct methods and refined to an R-value of 0.054 for 871 reflections with I greater than 2 sigma. The molecule exists as a zwitterion in the crystal. The peptide unit is trans and shows significant deviations from planarity (delta omega = 12.4 degrees). The peptide backbone adopts an extended conformation. The unit cell contains D-Ala-L-norval and its enantiomer. The molecular conformation and packing features show a striking resemblance to those for D-Ala-L-Met (1), and leads to the speculation that norvaline might act as an analog of methionine.

Dipeptides↗
PubMed1986

Structure and conformation of linear peptides. V. Structure of L-prolyl-glycyl-glycine.

The tripeptide, L-prolyl-glycyl-glycine, crystallizes in the trigonal space group P3(2), with a = b = 8.682(2) A, c = 12.008(2) and Z = 3. The structure was solved by direct methods and refined to an R-value of 0.07 for 727 reflections (I greater than 1.0 sigma). The molecule exists as a zwitterion in the crystal. The peptide units are trans and show significant deviations from planarity (omega 1 = 169.7 degrees, omega 2 = -170.1 degrees). The peptide backbone adopts a left-handed helical conformation similar to that of polyglycine II and polyproline II.

Amino Acid Sequence↗