The M-Superfamily of Conotoxins: A Review

Throughout the world there exist both predator and prey. This distinction is apparent though sometimes misleading. Take for example marine snails of the genus Conus that are present across the oceans of the southern hemisphere [1]. These snails are slow moving animals that appear more prey than predator. However, they have evolved into effective predators through the development of venom consisting of biologically active peptides. The venom is loaded into a hollow harpoon that the snail injects into the intended prey: fish, worms, or other snails [2]. The categories of cone snails based on prey preference are piscivorous (fish eating), molluscivorous (mollusk eating), and vermivorous (worm eating) [3]. The cone snail venom contains myriad peptide components significant to the survival of the organism with respect to hunting and defense against being eaten [4]. Interest by researchers in snails of the genus Conus began in the early nineteen seventies as evidence of their involvement in numerous human fatalities mounted [5]. Dr. Alan Kohn, an early pioneer in the study of hunter/prey relationship of cone snails, recognized that the venom of cone snails may possess therapeutic components [6]. During that time, Dr. Robert Endean and coworkers in Australia demonstrated that the venom of dissimilar species of cone snail contained a diversity of biologically active components. Dr. Baldomero (Toto) Olivera and coworkers at the University of Utah became the primary innovators of successful laboratory techniques in the study of venom components extracted from cone snails [7]. Foremost among these innovations was an avant-garde method of bio-assay using intracranial rather than intraperitoneal injection of toxin into subject mice. This new delivery method revealed greater sensitivity to individual peptides in fish and mouse studies than those from standard M-superfamily intraperitoneal injections [8]. This early research revealed the disulfide rich nature of the majority of peptide components from Conus snail venom. The disulfide rich peptides became broadly defined as conotoxins [9]

Minor Fibrillar Collagens, Variable Regions Alternative Splicing, Intrinsic Disorder, and Tyrosine Sulfation

Minor fibrillar collagen types V and XI, are those less abundant than the fibrillar collagens types I, II and III. The alpha chains share a high degree of similarity with respect to protein sequence in all domains except the variable region. Genomic variation and, in some cases, extensive alternative splicing contribute to the unique sequence characteristics of the variable region. While unique expression patterns in tissues exist, the functions and biological relevance of the variable regions have not been elucidated. In this review, we summarize the existing knowledge about expression patterns and biological functions of the collagen types V and XI alpha chains. Analysis of biochemical similarities among the peptides encoded by each exon of the variable region suggest the potential for shared function. The alternative splicing, conservation of biochemical characteristics in light of low sequence conservation, and evidence for intrinsic disorder, suggests modulation of binding events between the surface of collagen fibrils and surrounding extracellular molecules as a shared function

In situ ozone data for comparison with laser absorption remote sensor: 1980 PEPE/NEROS program

Several sets of in situ ozone (O3) measurements were made by a NASA aircraft in support of the laser absorption spectrometer (LAS) remote sensor. These measurements were designed to provide comparative O3 data for the LAS sensor. The LAS, which was flown on a second aircraft, remotely measured the vertical burden of O3 from the aircraft to the surface. In situ results of the air quality (O3 and B sub scat) and meteorological (temperature and dewpoint) parameters for three correlative missions are presented. The aircraft flight plans, in situ concentration profiles and vertical burdens, and measurement errors are summarized

DockoMatic - Automated Ligand Creation and Docking

Background: The application of computational modeling to rationally design drugs and characterize macro biomolecular receptors has proven increasingly useful due to the accessibility of computing clusters and clouds. AutoDock is a well-known and powerful software program used to model ligand to receptor binding interactions. In its current version, AutoDock requires significant amounts of user time to setup and run jobs, and collect results. This paper presents DockoMatic, a user friendly Graphical User Interface (GUI) application that eases and automates the creation and management of AutoDock jobs for high throughput screening of ligand to receptor interactions. Results: DockoMatic allows the user to invoke and manage AutoDock jobs on a single computer or cluster, including jobs for evaluating secondary ligand interactions. It also automates the process of collecting, summarizing, and viewing results. In addition, DockoMatic automates creation of peptide ligand .pdb files from strings of single-letter amino acid abbreviations. Conclusions: DockoMatic significantly reduces the complexity of managing multiple AutoDock jobs by facilitating ligand and AutoDock job creation and management

Oncostatin M Binds to Extracellular Matrix in a Bioactive Conformation: Implications for Inflammation and Metastasis

Oncostatin M (OSM) is an interleukin-6-like inflammatory cytokine reported to play a role in a number of pathological processes including cancer. Full-length OSM is expressed as a 26 kDa protein that can be proteolytically processed into 24 kDa and 22 kDa forms via removal of C-terminal peptides. In this study, we examined both the ability of OSM to bind to the extracellular matrix (ECM) and the activity of immobilized OSM on human breast carcinoma cells. OSM was observed to bind to ECM proteins collagen types I and XI, laminin, and fibronectin in a pH-dependent fashion, suggesting a role for electrostatic bonds that involves charged amino acids of both the ECM and OSM. The C-terminal extensions of 24 kDa and 26 kDa OSM, which contains six and thirteen basic amino acids, respectively, enhanced electrostatic binding to ECM at pH 6.5–7.5 when compared to 22 kDa OSM. The highest levels of OSM binding to ECM, though, were observed at acidic pH 5.5, where all forms of OSM bound to ECM proteins to a similar extent. This indicates additional electrostatic binding properties independent of the OSM C-terminal extensions. The reducing agent dithiothreitol also inhibited the binding of OSM to ECM suggesting a role for disulfide bonds in OSM immobilization. OSM immobilized to ECM was protected from cleavage by tumor-associated proteases and maintained activity following incubation at acidic pH for extended periods of time. Importantly, immobilized OSM remained biologically active and was able to induce and sustain the phosphorylation of STAT3 in T47D and ZR-75-1 human breast cancer cells over prolonged periods, as well as increase levels of STAT1 and STAT3 protein expression. Immobilized OSM also induced epithelial–mesenchymal transition-associated morphological changes in T47D cells. Taken together, these data indicate that OSM binds to ECM in a bioactive state that may have important implications for the development of chronic inflammation and tumor metastasis