Role of invariant water molecules in retaining the active site geometry of β-lactamase: a molecular dynamics simulation study

Water molecules play a critical role in stabilising the three-dimensional architecture, dynamics and function of biological macromolecules. Comparative analysis of structurally similar proteins has shown that there are water molecules conserved in the same relative positions and make similar hydrogen bonds with proteins in all crystal structures. These invariant water molecules are essential for the maintenance of the native structure of proteins. The present study explores the role of invariant water molecules to maintain the active site geometry of β-lactamase enzyme. Thirteen crystal structures of class-A β-lactamase from Staphylococcus aureus have been used in this study. Molecular dynamics simulations of the protein structures were performed in hydrated as well as in dehydrated conditions. The analysis showed that significant changes occur in the active site geometry due to dehydration. These changes can be attributed to the removal of water molecules at the active site.     

Polarized expression of type I phosphodiesterases in epithelial cells]

Type I phosphodiesterases are differently expressed by different cell types. Three members have been identified, PC-1, B10 and autotaxin. They are between 40 and 50% identical at the amino acid sequence level. Hepatocytes express both B10 and PC-1 at their plasma membrane. However, B10 is exclusively expressed at the apical pole whereas PC-1 is located at the basolateral pole. Studies of the biosynthetic route of B10 in hepatocytes shows that B10 is first transported to the basolateral surface and secondarily reaches the basolateral surface. The transcytotic step between the basolateral and apical surface occurs through a tubular endosomal compartment identical to the transcytotic compartment of the polymeric IgA receptor. Transfected in the polarized cell lines MDCK and Caco-2 of renal and intestinal origin, B10 and PC-1 are expressed at the apical and basolateral poles respectively, as in hepatocytes. However, the biosynthetic transport of B10 occurs directly in MDCK cells and both directly and by transcytosis in Caco-2 cells. Truncation of the cytoplasmic domain of PC-1 generates an apical protein indicating that the basolateral signal of PC-1 is likely to be in the cytoplasmic domain. The nature of the apical targeting signal of B10 is under investigation.     

Systems biology of pathogen-host interaction: Networks of protein-protein interaction within pathogens and pathogen-human interactions in the post-genomic era

Infectious diseases comprise some of the leading causes of death and disability worldwide. Interactions between pathogen and host proteins underlie the process of infection. Improved understanding of pathogen-host molecular interactions will increase our knowledge of the mechanisms involved in infection, and allow novel therapeutic solutions to be devised. Complete genome sequences for a number of pathogenic microorganisms, as well as the human host, has led to the revelation of their protein-protein interaction (PPI) networks. In this post-genomic era, pathogen-host interactions (PHIs) operating during infection can also be mapped. Detailed systematic analyses of PPI and PHI data together are required for a complete understanding of pathogenesis of infections. Here we review the striking results recently obtained during the construction and investigation of these networks. Emphasis is placed on studies producing large-scale interaction data by high-throughput experimental techniques.     

Experimental-based mechanobiological modeling of the anabolic and catabolic effects of breast cancer on bone remodeling

Biomechanics and Modeling in Mechanobiology - Bone is a biological tissue characterized by its hierarchical organization. This material has the ability to be continually renewed, which makes it...