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Energy barriers and rates of tautomeric transitions in DNA bases: Ab initio quantum chemical study

Thu, 01 Dec 2005 00:00:00 GMT

Title: Energy barriers and rates of tautomeric transitions in DNA bases: Ab initio quantum chemical study Authors: Basu, Soumalee; Majumdar, Rabi; Das, Gourab K; Bhattacharyya, Dhananjay Abstract: Tautomeric transitions of DNA bases are proton transfer reactions, which are important in biology. These reactions are involved in spontaneous point mutations of the genetic material. In the present study, intrinsic reaction coordinates (IRC) analyses through ab initio quantum chemical calculations have been carried out for the individual D A bases A, T, G, C and also A:T and G:C base pairs to estimate the kinetic and thermodynamic barriers using MP2/6-31G** method for tautomeric transitions. Relatively higher values of kinetic barriers (about 50-60 kcal/mol) have been observed for the single bases, indicating that tautomeric alterations of isolated single bases are quite unlikely. On the other hand, relatively lower values of the kinetic barriers (about 20-25 kcal/mol) for the DNA base pairs A:T and G:C clearly suggest that the tautomeric shifts are much more favorable in DNA base pairs than in isolated single bases. The unusual base pairing A':C, T':G, C':A or G':T in the daughter DNA molecule, resulting from a parent DNA molecule with tautomeric shifts, is found to be stable enough to result in a mutation. The transition rate constants for the single DNA bases in addition to the base pairs are also calculated by computing the free energy differences between the transition states and the reactants. Page(s): 378-385

Evaluation of hepatoprotective potential of propolis extract in carbon tetrachloride induced liver injury in rats

Sat, 01 Oct 2005 00:00:00 GMT

Title: Evaluation of hepatoprotective potential of propolis extract in carbon tetrachloride induced liver injury in rats Authors: Shukla, Sangeeta; Bhadauria, Monika; Jadon, Anjana Abstract: Propolis (bee glue), a resinous wax-like beehive product has been used since ancient times for its pharmaceutical properties. In the present study, the ethanolic extract of propolis (50, 100, 200 and 400 mg/kg, p.o.) was studied for its hepatoprotective activity against carbon tetrachloride (CC1₄, 1.5 ml/kg, i.p.) induced liver damage in rats. Administration of CCl₄ caused a sharp elevation in the activity of serum transaminases, serum alkaline phosphatase, acid phosphatase and hepatic lipid peroxidation (LPO) levels, and a significant decrease in the ATPase, alkaline phosphatase and succinic dehydrogenase activities in the liver and kidney and hepatic GSH level. The treatment with propolis extract at the doses of 200 and 400 mg/kg significantly reversed the various biochemical alterations in blood, liver and kidney induced by CCl₄ intoxication. The hepatoprotective property of propolis maybe due to its antioxidant activity. Page(s): 321-325

Purification and characterization of α-amylase from Bacillus amyloliquefaciens NCIM 2829

Sat, 01 Oct 2005 00:00:00 GMT

Title: Purification and characterization of α-amylase from Bacillus amyloliquefaciens NCIM 2829 Authors: De, Mithu; Das, Kali P; Chakrabartty, P K Abstract: α-Amylase (EC 3.2.1.1) was purified to homogeneity (specific activity 58,000 µmole min^-1 mg protein^-1) from the culture filtrate of Bacillus amyloliquefaciens NCIM 2829. Its molecular mass was found to be 67.5 kDa. The activity of the enzyme increased by almost 50% in the presence of Co⁺² ion. Hg⁺² and Cu⁺² acted as strong inhibitors of the enzyme. The tryptophan moities of the enzyme were fairly protected from the aqueous environment. However, the globular interior of the protein was somewhat loosely packed. The protein had nearly an equal amount of α-helical and β-sheet structure in dilute solution. In concentrated solution, its secondary structure had a higher proportion of β-sheet at the expense of some random coil structure. The protein showed a molten globule state at a low concentration of chaotropic agent. The denaturation profile of the protein showed no cooperativity. Co²⁺ enhanced the structural stability of the enzyme. Page(s): 287-294

Crystal structure of a novel phospholipase A₂ from crude venom of Indian cobra sub-species Naja naja sagittifera at 1.48 Ǻ resolution

Sat, 01 Oct 2005 00:00:00 GMT

Title: Crystal structure of a novel phospholipase A₂ from crude venom of Indian cobra sub-species Naja naja sagittifera at 1.48 Ǻ resolution Authors: Singh, Rajendra K; Jabeen, Talat; Sharma, Sujata; Kaur, Punit; Srinivasan, A; Singh, Tej P Abstract: Secretory phospholipase A₂s (PLA₂s), the structurally-homologous enzymes share a common qualitative catalytic site, but differ greatly in their pharmacological properties and toxicities. There has been a recognizable pattern of mutations in the primary sequence of PLA₂s that alter their catalytic properties significantly. In the present study, the amino acid sequence and the three-dimensional structure of a new isoform of PLA₂ from crude venom of Indian cobra sub-species Naja naja sagittijera (N.n.s.) has been determined by X-ray crystallography. The crystal structure has revealed several novel features of PLA₂ folding and furiction. It contains 913 protein atoms and one each of Ca²⁺, phosphate and acetate ions with 142 solvent water molecules. A Ca²⁺ ion is present in the calcium-binding loop and forms a seven-fold coordination with a distorted" pentagonal bipyramidal geometry. One of the coordination linkages is with the acetate ion, instead of the conserved water molecule. The presence of Lys at position 31 has a stabilizing effect on the loop Tyr 25-Cys 29 by interacting 'with carbonyl oxygen atoms of Tyr 25, Gly 26 and Cys 29. In turn, it lends stability to the Ca²⁺-binding loop as well. Another unique feature of the PLA₂ structure is the formation of an intrastrand hydrogen bond, involving Oγ of Thr 73 and Oɛ2 of Glu 71, thus helping the β-wing to act as a sharp arrow for insertion into other molecules. Yet another important feature of this PLA₂ pertains to the conformation of its C-terminal segment, which is stabilized by a unique hydrogen bond through carbonyl oxygen of Lys 116 and Nδ2 of Asn 120. This structural feature may be useful in the molecular recognition of the PLA₂ through C-terminal segment. Page(s): 279-286

NOPR Community:

Energy barriers and rates of tautomeric transitions in DNA bases: Ab initio quantum chemical study

Evaluation of hepatoprotective potential of propolis extract in carbon tetrachloride induced liver injury in rats

Purification and characterization of α-amylase from Bacillus amyloliquefaciens NCIM 2829

Crystal structure of a novel phospholipase A2 from crude venom of Indian cobra sub-species Naja naja sagittifera at 1.48 Ǻ resolution

Crystal structure of a novel phospholipase A₂ from crude venom of Indian cobra sub-species Naja naja sagittifera at 1.48 Ǻ resolution