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Summary: The non‐specific lipid transfer proteins (nsLTPs) are multifunctional seed proteins engaged in several different physiological processes. The nsLTPs are stabilized by four disulfide bonds and exhibit a characteristic hydrophobic cavity, which is the primary lipid binding site. While these proteins are known to transfer lipids between membranes, the mechanism of lipid transfer has remained elusive. Four crystal structures of nsLTP from Solanum melongena, one in the apo‐state and three myristic acid bound states were determined. Among the three lipid bound states, two lipid molecules were bound on the nsLTP surface at different positions and one was inside the cavity. The lipid‐dependent conformational changes leading to opening of the cavity were revealed based on structural and spectroscopic data. The surface‐bound lipid represented a transient intermediate state and the lipid ultimately moved inside the cavity through the cavity gate as revealed by molecular dynamics simulations. Two critical residues in the loop regions played possible 'gating' role in the opening and closing of the cavity. Antifungal activity and membrane permeabilization effect of nsLTP against Fusarium oxysporum suggested that it could possibly involve in bleaching out the lipids. Collectively, these studies support a model of lipid transfer mechanism by nsLTP via intermediate states. Significance Statement: A model of lipid transfer mechanism of nsLTP from Solanum melongena has been proposed through intermediate crystal structures with lipid bound at different sites. [ABSTRACT FROM AUTHOR]

Determination of sex constitutes the most important element during the identification process of human skeletal remains. Several sex-specific features of human skeleton have been exploited for sex determination with varying reliability. This study aims to obtain sexual dimorphic standards for ulnae of the north Indian population. Eight measurements were obtained on a sample of 106 ulnae (males-80, females-26) in the age range of 25-65 years. The sexual dimorphism index and demarking points were calculated for all the variables. The data were then subjected to stepwise and direct discriminant function analysis. The best discriminator of sex was the maximum length (84.9%) followed by radial notch width (84%). In stepwise analysis, these two variables were selected and provided an accuracy of 88.7% (M-87.5%, F-92.3%). The proximal end provided a classification rate of 81.1% (M-80%, F-84.6%) with selection of the notch length and olecranon width. [ABSTRACT FROM AUTHOR]

Cyclin-dependent kinases (CDKs) are core components of the cell cycle machinery that govern the transition between phases during cell cycle progression. Abnormalities in CDKs activity and regulation are common features of cancer, making CDK family members attractive targets for the development of anticancer drugs. Their inhibitors have entered in clinical trials to treat cancer. Very recently, Heathcote et al. (J. Med. Chem. 2010, 53:8508-8522) have found a ligand BS194 that has a high affinity with CDK2 (IC50 = 3 n m) but shows low affinity with CDK1 (IC50 = 30 n m). To understand the selectivity, we used homology modeling, molecular docking, molecular dynamics, and free-energy calculation to analyze the interactions. A rational three-dimensional model of the CDK1/BS194 complex is built. We found that Leu83 is a key residue that recognizes BS194 more effectively with CDK2 with good binding free energies rather than CDK1. Energetic analysis reveals that van der Waals interaction and non-polar contributions to solvent are favorable in the formation of complexes and amine group of the ligand, which plays a crucial role for binding selectivity between CDK2 and CDK1. Copyright © 2012 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]