Macromolecular crowding modulates folding mechanism of alpha/beta protein apoflavodoxin

Protein dynamics in cells may be different from that in dilute solutions in vitro since the environment in cells is highly concentrated with other macromolecules. This volume exclusion due to macromolecular crowding is predicted to affect both equilibrium and kinetic processes involving protein conformational changes. To quantify macromolecular crowding effects on protein folding mechanisms, here we have investigated the folding energy landscape of an alpha/beta protein, apoflavodoxin, in the presence of inert macromolecular crowding agents using in silico and in vitro approaches. By coarse-grained molecular simulations and topology-based potential interactions, we probed the effects of increased volume fraction of crowding agents (phi_c) as well as of crowding agent geometry (sphere or spherocylinder) at high phi_c. Parallel kinetic folding experiments with purified Desulfovibro desulfuricans apoflavodoxin in vitro were performed in the presence of Ficoll (sphere) and Dextran (spherocylinder) synthetic crowding agents. In conclusion, we have identified in silico crowding conditions that best enhance protein stability and discovered that upon manipulation of the crowding conditions, folding routes experiencing topological frustrations can be either enhanced or relieved. The test-tube experiments confirmed that apoflavodoxin's time-resolved folding path is modulated by crowding agent geometry. We propose that macromolecular crowding effects may be a tool for manipulation of protein folding and function in living cells.Comment: to appear in Biophysical Journal (2009). to appear in Biophysical Journal (2009

Genus Blepharis (Acanthaceae): A review of ethnomedicinally used species, and their phytochemistry and pharmacological activities.

ETHNOPHARMACOLOGICAL RELEVANCE:Blepharis is an Afro-Asiatic genus belonging to the family Acanthaceae. It comprises 126 species that occur in arid and semi-arid habitats. Some species of Blepharis are used in traditional medicines in different countries mainly for their anti-inflammatory, would healing activities along with treatment of gastrointestinal disorders and bone fractures. AIM OF THE REVIEW:The present review aims to collate and analyze the available data and information on distribution, traditional uses, chemical constituents and pharmacological activities of Blepharis. METHODS:Scientific information of genus Blepharis was retrieved from the online bibliographic databases like MEDLINE/PubMed, SciFinder, Web of Science and Google Scholar and secondary resources including books and proceedings. RESULTS:Seven species of Blepharis were found to be reported frequently as useful in folklore in Asian and African countries. B. maderaspatensis was found to be widely used in Indian traditional medicines whereas the B. ciliaris and B. edulis were common in folklore of Egypt, Jordan, and Arabia. Active phytochemicals of Blepharis are flavonoids from B. ciliaris, alkaloids from B. sindica, phenolic acid derivatives, and phytosterols, and derivatives of hydroxamic acids from B. edulis resulted in possessing diverse biological properties such as anti-microbial, anti-inflammatory, and anti-cancer. CONCLUSION:Various species of Blepharis were found to be used in traditional medicine systems in African and Asian countries. Few of these species were studied for their bioactive chemical constituents however the activity guided isolation studies are not performed. Similarly, detailed pharmacological studies in animal models to explore their mechanism of action are also not reported. Future studies should focus on these aspects related to the medicinally used species of Blepharis. The detailed and comprehensive comparative analysis presented here gives valuable information of the currently used Blepharis species and pave the way to investigate other useful species of Blepharis pertaining to ethnobotany, phytochemistry and discovery of new drugs

Bioactive Compounds from Zingiber montanum and Their Pharmacological Activities with Focus on Zerumbone

The genus Zingiber consists of about 85 species and many of these species are used as food, spices, and medicines. One of the species, Zingiber montanum (J. Koenig) Link ex A. Dietr. is native to Southeast Asia and has been extensively used as traditional medicines and food. The aim of this review was to collect and critically analyze the scientific information about the bioactive compounds and pharmacological activities of Z. montanum with focus on one of the main components, zerumbone (ZER). Various studies have reported the analysis of volatile constituents of the essential oils from Z. montanum. Similarly, many phenylbutanoids, flavonoids and terpenes were also isolated from rhizomes. These essential oils, extracts and compounds showed potent antimicrobial, anti-inflammatory and antioxidant activities among others. Zerumbone has been studied widely for its anticancer, anti-inflammatory, and other pharmacological activities. Future studies should focus on the exploration of various pharmacological activities of other compounds including phenylbutanoids and flavonoids. Bioassay guided isolation may result in the separation of other active components from the extracts. Z. montanum could be a promising source for the development of pharmaceutical products and functional foods.</jats:p