Induced cycles in triangle graphs

The triangle graph of a graph $G$, denoted by ${\cal T}(G)$, is the graph whose vertices represent the triangles ($K_3$ subgraphs) of $G$, and two vertices of ${\cal T}(G)$ are adjacent if and only if the corresponding triangles share an edge. In this paper, we characterize graphs whose triangle graph is a cycle and then extend the result to obtain a characterization of $C_n$-free triangle graphs. As a consequence, we give a forbidden subgraph characterization of graphs $G$ for which ${\cal T}(G)$ is a tree, a chordal graph, or a perfect graph. For the class of graphs whose triangle graph is perfect, we verify a conjecture of the third author concerning packing and covering of triangles.Comment: 27 page

Exploring the Structure of Opioid Receptors with Homology Modeling based on Single and Multiple Templates and Subsequent Docking: A Comparative Study

Opioid receptors are the principal targets for opioids, which have been used as analgesics for centuries. Opioid receptors belong to the rhodopsin family of G-protein coupled receptors (GPCRs). In the absence of crystal structures of opioid receptors, 3D homology models have been reported with bovine rhodopsin as a template, though the sequence homology is low. Recently, it has been reported that use of multiple templates results in a better model for a target having low sequence identity with a single template. With the objective of carrying out a comparative study on the structural quality of the 3D models based on single and multiple templates, the homology models for opioid receptors (mu, delta and kappa) were generated using bovine rhodopsin as single template and the recently deposited crystal structures of squid rhodopsin, turkey β-1 and human β-2 adrenoreceptors along with bovine rhodopsin as multiple templates. In this paper we report the results of comparison between the refined 3D models based on multiple sequence alignment (MSA) and models built with bovine rhodopsin as template, using validation programs PROCHECK, PROSA, Verify 3D, Molprobity and docking studies. The results indicate that homology models of mu and kappa with multiple templates are better than those built with only bovine rhodopsin as template, whereas, in many aspects, the homology model of delta opioid receptor with single template is better with respect to the model based on multiple templates. Three nonselective ligands were docked to both the models of mu, delta and kappa opioid receptors using GOLD 3.1. The results of docking complied well with the pharamacophore, reported for nonspecific opioid ligands. The comparison of docking results for models with multiple templates and those with single template have been discussed in detail. Three selective ligands for each receptor were also docked. As the crystallographic structures are not yet known, this comparison will help in choosing better homology models of opioid receptors for studying ligand receptor interactions to design new potent opioid antagonists

Prospective microglia and brain macrophage distribution pattern in normal rat brain shows age sensitive dispersal and stabilization with development

561-567The monocytic lineage cells in brain, generally speaking brain macrophage and/or microglia show some dissimilar distribution patterns and disagreement regarding their origin and onset in brain. Here, we investigated its onset and distribution/colonization pattern in normal brain with development. Primarily, early and late embryonic stages, neonate and adult brains were sectioned for routine H/E staining; a modified silver-gold staining was used for discriminating monocytic lineage cells in brain; and TEM to deliver ultramicroscopic details of these cells in brain. Immunofluorescence study with CD11b marker revealed the distribution of active microglia/macrophage like cells. Overall, in early embryonic day 12, the band of densely stained cells are found at the margin of developing ventricles and cells sprout from there dispersed towards the outer edge. However, with development, this band shrunk and the dispersion trend decreased. The deeply stained macrophage like cell population migration from outer cortex to ventricle observed highest in late embryonic days, continued with decreased amount in neonates and settled down in adult. In adult, a few blood borne macrophage like cells were observed through the vascular margins. TEM study depicted less distinguishable features of cells in brain in early embryo, whereas from late embryo to adult different neuroglial populations and microglia/macrophages showed distinctive features and organization in brain. CD11b expression showed some similarity, though not fully, with the distribution pattern depending on the differentiation/activation status of these macrophage lineage cells. This study provides some generalized spatial and temporal pattern of macrophage/microglia distribution in rat brain, and further indicates some intrigue areas that need to be addressed

Simultaneous Parallel and Antiparallel Self-Assembly in a Triazole/Amide Macrocycle Conformationally Homologous to D-,L-r-Amino Acid Based Cyclic Peptides: NMR and Molecular Modeling Study.

A 1,4-linked triazole/amide based peptidomimetic macrocycle, synthesized from a triazole amide oligomer of cis-furanoid sugar triazole amino acids, possesses a conformation resembling the D-,L-R-amino acid based cyclic peptides despite having uniform backbone chirality. It undergoes a unique mode of self-assembly through an antiparallel backbone to backbone intermolecular H-bonding involving amide NH and triazole N2/N3 as well as parallel stacking via amide NH and carbonyl oxygen H-bonding, leading to the formation of a tubular nanostructure

Expression and molecular characterization of the Mycobacterium tuberculosis PII protein

The signal transduction protein PII plays an important role in cellular nitrogen assimilation and regulation. The molecular characteristics of the Mycobacterium tuberculosis PII (Mtb PII) were investigated using biophysical experiments. The Mtb PII coding ORF Rv2919c was cloned and expressed in Escherichia coli. The binding characteristics of the purified protein with ATP and ADP were investigated using surface plasmon resonance (SPR) and isothermal titration calorimetry (ITC). Mtb PII binds to ATP strongly with Kd in the range 1.93–6.44 μM. This binding strength was not significantly affected by the presence of 2-ketoglutarate even in molar concentrations of 66 (ITC) or 636 (SPR) fold excess of protein concentration. However, an additional enthalpy of 0.3 kcal/mol was released in presence of 2-ketoglutarate. Binding of Mtb PII to ADP was weaker by an order of magnitude. Binding of ATP and 2-ketoglutarate were analysed by docking studies on the Mtb PII crystal structure (PDB id 3BZQ). We observed that hydrogen bonds involving the γ-phosphate of ATP contribute to enhanced binding of ATP compared with ADP. Glutaraldehyde crosslinking showed that Mtb PII exists in homotrimeric state which is consistent with other PII proteins. Phylogenetic analysis showed that Mtb PII consistently grouped with other actinobacterial PII proteins

Modeling and structural analysis of PA clan serine proteases

<p>Abstract</p> <p>Background</p> <p>Serine proteases account for over a third of all known proteolytic enzymes; they are involved in a variety of physiological processes and are classified into clans sharing structural homology. The PA clan of endopeptidases is the most abundant and over two thirds of this clan is comprised of the S1 family of serine proteases, which bear the archetypal trypsin fold and have a catalytic triad in the order Histidine, Aspartate, Serine. These proteases have been studied in depth and many three dimensional structures have been experimentally determined. However, these structures mostly consist of bacterial and animal proteases, with a small number of plant and fungal proteases and as yet no structures have been determined for protozoa or archaea. The core structure and active site geometry of these proteases is of interest for many applications. This study investigated the structural properties of different S1 family serine proteases from a diverse range of taxa using molecular modeling techniques.</p> <p>Results</p> <p>Our predicted models from protozoa, archaea, fungi and plants were combined with the experimentally determined structures of 16 S1 family members and used for analysis of the catalytic core. Amino acid sequences were submitted to SWISS-MODEL for homology-based structure prediction or the LOOPP server for threading-based structure prediction. Predicted models were refined using INSIGHT II and SCRWL and validated against experimental structures. Investigation of secondary structures and electrostatic surface potential was performed using MOLMOL. The structural geometry of the catalytic core shows clear deviations between taxa, but the relative positions of the catalytic triad residues were conserved. Some highly conserved residues potentially contributing to the stability of the structural core were identified. Evolutionary divergence was also exhibited by large variation in secondary structure features outside the core, differences in overall amino acid distribution, and unique surface electrostatic potential patterns between species.</p> <p>Conclusions</p> <p>Encompassing a wide range of taxa, our structural analysis provides an evolutionary perspective on S1 family serine proteases. Focusing on the common core containing the catalytic site of the enzyme, this analysis is beneficial for future molecular modeling strategies and structural analysis of serine protease models.</p

Transient overexpression ofWerner protein rescues starvation induced autophagy inWerner syndrome cells

Reduced autophagy may be associated with normal and pathological aging. Here we report a link between autophagy and Werner protein (WRNp), mutated in Werner syndrome, the human premature aging Werner syndrome (WS).WRNmutant fibroblast AG11395 and AG05229 respondweakly to starvation induced autophagy compared to normal cells. While the fusion of phagosomes with lysosome is normal, WS cells contain fewer autophagy vacuoles. Cellular starvation autophagy in WS cells is restored after transfection with full length WRN. Further, siRNA mediated silencing of WRN in the normal fibroblast cell line WI-38 results in decreased autophagy and altered expression of autophagy related proteins. Thus, our observations suggest that WRN may have a role in controlling autophagy and hereby cellular maintenance