Primary Hyperoxaluria Type 1 with Homozygosity for a Double-mutated AGXT Allele in a 2-year-old Child.

Primary hyperoxaluria (PH) Type 1 is a rare, genetic disorder caused by deficiency of the liver enzyme alanine-glyoxylate aminotransferase, which is encoded by AGXT gene. We report a 2-year-old South Indian Tamil child with nephrocalcinosis due to PH Type 1, in whom a homozygous genotype for two missense mutations in the AGXT gene was found: first, a C to G transversion (c. 32C>G) in exon 1 resulting in the amino acid substitution p.Pro11Arg; second, a T to A transversion (c. 167T>A) in exon 2 resulting in p.Ile56Asn. A therapy based on potassium citrate and pyridoxine was started. This is the first report of molecular testing-proven childhood onset-PH Type 1 from South India and is notable for the co-occurrence of two missense mutations in one AGXT allele, which might lead to different and more severe phenotype than each mutation alone. To the best of our knowledge, AGXT allele carrying two already known mutations has not been previously reported.

Management of bio-medical waste: awareness and practices in a district of Gujarat.

With the objective of assessing the level of awareness about the various aspects of biomedical waste and disposal practices by the medical practitioners this study was conducted. It was a cross sectional study. 30 hospitals with more than 30 beds minimum were randomly selected from Sabarkantha district, Gujarat. The doctors and auxiliary staff of those 30 hospitals were the study population. While all the doctors knew about the existence of the law related to biomedical waste but details were not known. Doctors were aware of risk of HIV and Hepatitis B and C, whereas auxiliary staff (ward boys, ayabens, sweepers) had very poor knowledge about it. There was no effective waste segregation, collection, transportation and disposal system at any hospital in the district. There is an immediate and urgent need to train and educate all doctors and the staff to adopt an effective waste management practices.

Isolation and structure (X-ray analysis) of ent-norsecurinine, an alkaloid from Phyllanthus niruri.

The isolation and structure determination of the alkaloid ent-norsecurinine (4) from Phyllanthus niruri L. is described. The structure and absolute stereochemistry have been confirmed by an X-ray analysis of ent-norsecurinine hydrochloride.

Calcium binding cyclic hexapeptide. Crystal structure of cyclo-(L-prolyl-glycyl)3 calcium complex.

The synthetic cyclic hexapeptide (L-prolyl-glycyl)3 forms a 2:1 complex with Ca2+ ion. The cation is sandwiched between the two peptide molecules. The glycyl carbonyls from each of the peptides are octahedrally coordinated to the cation with an average calcium oxygen coordination distance of 2.26A. Both the molecules coordinating to the calcium ion have three fold symmetry, but show significant conformational differences. In one of the peptides of the sandwich, the alternate carbonyls point to the opposite sides of the peptide ring while in the other, all the six carbonyls point to the same side of the ring. Three NH ... O hydrogen bonds between the peptides add to the stability of the sandwich.

Crystal and molecular structure of cyclo(L-prolyl-glycyl)3. A cyclic hexapeptide with a cis peptide bond.

The crystal structure of cyclo(L-Pro-Gly)3 was solved using X-ray crystallographic techniques. The backbone of the peptide is asymmetric and is made up of five trans peptide units and one cis peptide. There is a hydrogen bonded water bridge that links the carbonyl oxygens, O1 and O4. The molecules exist as dimers in the crystal lattice. The two molecules of the dimer are related by crystallographic twofold symmetry and are linked by two N-H ... O hydrogen bonds. The crystals are trigonal, space group P3(2)12 with a = 11.379(3), c = 32.93(1) and z = 6. The structure was solved by multisolution methods and refined by least squares technique to an R of 0.083.

Modified steroid hormones. 7. 4-Fluoro-17 beta-estradiol: carbon-13 nuclear magnetic resonance, crystal and molecular structure, and biological activity.

The 4-fluoro analogue of 17 beta-estradiol was investigated for estrogenic action in rats by determination of uterine hyperemia and [3H]uridine incorporation and was found to be an active estrogen. Antitumor activity of this analogue was demonstrated against 7,12-dimethylbenz[a]anthracene (DMBA) induced rat mammary adenocarcinoma. Its 13C NMR spectrum was determined, and all signals were assigned. A detailed X-ray diffraction investigation of 4-fluoro-17 beta-estradiol was carried out, and it crystallized in triclinic space group P1 with two steroids and one methanol in a unit cell of a = 7.367 (1), b = 9.363 (6), c = 12.531 (1) A, alpha = 89.31 (3), beta = 93.38 (1), gamma = 109.62 (3) degrees, V = 812.8 A3, and Z = 2. The structure was solved and refined to an R index of 0.062 using 3045 reflections measured on an automated diffractometer. The oxygen atoms at C(3) and C(17) at either ends link the molecules together in a head to tail fashion. The hydroxy groups of the solvent molecules also take part in linking the molecules sideways through the hydroxy groups.

Conformation of cyclo(-L-Pro-Gly-)(3) and its Ca and Mg complexes.

The synthetic hexapeptide cyclo(-L-Pro-Gly-)(3) is an ionophore that shows interesting conformational changes upon binding metal ions. X-ray crystallographic studies of this peptide show that when it is crystallized from an ethanol/ethyl acetate mixture the ring takes up an asymmetric conformation containing one cis peptide bond. In crystals of a Ca(2+) complex, the cation is sandwiched between two peptide molecules that differ markedly in conformation. However, both exhibit threefold symmetric forms, with all six peptide bonds in the molecule occurring in the usual trans conformation. The Ca(2+) is octahedrally surrounded by six glycyl carbonyl oxygens from the two peptides at an average distance of 2.26 A and can easily be released by the disruption of the peptide sandwich. In the magnesium complex, the peptide forms a 1:1 complex with the ion. The Mg(2+) is octahedrally coordinated to three glycyl carbonyls and three water oxygens. The average coordination distance between magnesium and the peptide oxygens is 2.03 A and that between magnesium and water oxygen is 2.11 A. The two peptide molecules in the asymmetric unit have similar conformations and have approximate threefold symmetry.

Crystal and molecular structure of the antibiotic blasticidin S hydrochloride pentahydrate.

The three-dimensional structure of blasticidin S hydrochloride pentahydrate, a member of the cytosine amino nucleoside antibiotics, has been solved using diffractometer data and refined to an R value of 0.115. The crystal data are a = 13.500(5), b = 20.387(7), c = 4.824 A, beta = 98.66(3) degrees, Z = 2, Dc = 1.389 g .cm-3, space group P21. The nucleoside base conformation is anti(chi = 86 degrees) and the 2',3'-unsaturated pyranosyl sugar exhibits a half-chair (degree H5) conformation. The amide plane is twisted from the trans position by about 10 degrees. The guanidium group and the amino group of the amino acid chain are positively charged, while the carboxyl group of the sugar is ionized. The chloride ion is surrounded by water molecules only, in a trigonal prismatic arrangement. The molecule has an extended conformation and there is an intramolecular hydrogen bond between the ammonium group and the carboxyl group. A striking feature of blasticidin is that all the hydrophilic groups lie on one side of the molecule and the hydrophobic groups on the other. Amicetin also shows a similar feature and this might be linked to the commonality of their antibiotic functions. Hydrogen bonds link the hydrophilic sides of adjacent molecules forming double chains parallel to the b-axis. The hydrophobic sides of adjacent double chains are separated by a water layer.

Crystal structure and conformation of cyclo-L-cystine.

X-ray crystallographic investigations on cyclo-L-cystine show that the diketopiperazine ring is in a twisted boat form and the C-S-S-C bridge across the C alpha atoms has a negative chirality with chi 3 angle of - 94 degrees, The two peptides are significantly nonplanar with the omega values of - 10 degrees and - 16 degrees. The crystals are orthorhombic, space group P212121 with a = 11.216(4), b = 12.874(4), c = 5.978(3) and Z = 4. The structure was solved by heavy atom method and refined to an R index of 0.065.

A new arylating agent, 2-carboxy-4,6-dinitrochlorobenzene. Reaction with model compounds and bovine pancreatic ribonuclease.

The reagent 2-carboxy-4,6-dinitrochlorobenzene (CDNCB) reacts with the imino, amino and sulfhydryl groups of model compounds. At pH 8.2, sulfhydryl groups react much faster than do amines. N alpha-Acetylhistidine, N alpha-acetyltyrosine and N alpha-acetyltryptophan do not react. Poly(L-Lysine) and poly(DL-lysine) react about 50 times as fast as does N alpha-acetyllysine. A dichloroanalog, 6-carboxy-2,4-dinitro-1,3-dichlorobenzene, shows stepwise reactivity with amines. With bovine pancreatic ribonuclease, which contains no sulfhydryl, CDNCB reacts preferentially with the epsilon-amino of Lys-41 at 450 times the rate with the epsilon-amino of N alpha-acetyllysine. The preferential reactivity at Lys-41 is discussed in relation to the pK of Ly-41, the cationic character of the active site cleft, and the mechanism of RNAase action on substrates.

Cytidylic acid "a" trihydrate: structure and conformation.

Cytidylic acid "a" (cytidine 2'-monophosphate) crystallizes in the triclinic space group P1 with two molecules of cytidine monophosphate (C(9)H(14)O(8)N(3)P) and six molecules of water in the unit cell. X-ray analysis of this crystal shows that in both molecules, the base is in the anti conformation, the ribose ring is C(2')-endo puckered, and the hydroxyl O(5') is gauche-gauche. The two molecules are linked by a short hydrogen bond through the phosphate oxygens.