Namita Surolia

De novo biosynthesis of heme offers a new chemotherapeutic target in the human malarial parasite

The human malarial parasite, Plasmodium falciparum, has been found to synthesize heme de novo, despite the accumulation of large quantities of polymeric heme derived from the hemoglobin of the red cell host. The parasite delta-aminolevulinate dehydrase level is significantly lower than that of the host and its inhibition by succinylacetone leads to inhibition of parasite protein synthesis and viability.

Kinetic and Thermodynamic Analysis of the Interactions of 23-Residue Peptides with Endotoxin

Many naturally occurring peptides exhibit lipopolysaccharide binding properties. In this work we describe the endotoxin binding properties of a series of 23-residue peptides based on the sequence corresponding to the antisense strand of themagainin gene. Biochemical and biophysical characterization of these peptides reveals that they have the tendency to perturb both the inner and outer membranes of test pathogens. Structurally these peptides are amphiphilic and adopt helical conformations in membranes. Three of the seven peptides tested have high affinities for endotoxin that approach the values shown by polymyxin B, a cyclic cationic acylated decapeptide, which is used clinically in treating extreme cases of sepsis. The kinetic parameters obtained using stopped-flow methods and BIAcoreTM analysis, when considered in conjunction with the isothermal titration calorimetry-derived thermodynamic parameters, allow us to highlight the key structural features essential for lipopolysaccharide (LPS) recognition by these peptides. The studies stress the role of ionic forces in the initial recognition of LPS. The fortification of the strength of these ionic charges increases affinity for LPS, whereas the hydrophobic residues involved in interactions are more amenable to disruptions in contiguity. Peptides that improve these features further are expected to perform better as endotoxin-neutralizing agents.

Mechanism of foetal wastage following immunoneutralization of riboflavin carrier protein in the pregnant rat: disturbances in flavin coenzyme levels

Immunoneutralization of maternal RCP results in a >90% decrease in the content and the incorporation of [2‐14C]riboflavin into embryonic FAD as well as a percentage redistribution of both embryonic FMN and riboflavin. This is unaccompanied by any discernible changes in flavin distribution pattern in the maternal liver. Embryonic α‐glycerophosphate dehydrogenase and NADPH‐cytochrome c reductase register significant decreases in activities in the RCP antiserum‐treated rats. These alterations readily explain the arrest of foetal growth culminating in pregnancy termination in the antiserum‐treated animals.

Crystallization and preliminary crystallographic analysis of beta-hydroxyacyl ACP dehydratase (FabZ) from Plasmodium falciparum.

The malarial parasite Plasmodium falciparum synthesizes fatty acids by the type II mechanism. In this cycle, the dehydration of the beta-hydroxyacyl acyl carrier protein is catalyzed by FabZ. Purified FabZ has been crystallized using the hanging-drop vapour-diffusion and microbatch techniques. The crystals are orthorhombic, with space group I222 or I2(1)2(1)2(1) and unit-cell parameters a = 71.78, b = 81.99, c = 97.49 A. A complete data set to a resolution of 2.5 A has been collected under cryoconditions (100 K) using a MAR imaging-plate detector system mounted on a rotating-anode X-ray generator.