Scientists discover new compounds that may alter the circadian rhythm -
Scientists of Florida campus of The Scripps Research Institute (TSRI) have discovered a surprising new role for compounds- pair who have the potential to alter the circadian rhythm, the complex physiological process that responds to a 24-hour cycle of light and dark and is present in most living beings.
at least one of these compounds could be developed as a chemical probe to discover new therapeutic approaches for a range of disorders, including diabetes and obesity.
study, which was printed before published online by the Journal of Biological Chemistry , focuses on a group of proteins called REV-ERB, a superfamily that plays an important role in the regulation of circadian physiology, metabolism and immune function.
The new study shows that the two compounds, cobalt protoporphyrin IX (COPP) and zinc protoporphyrin IX (ZnPP) bind directly to REV-ERB.
REV-ERB are normally regulated by heme, a molecule that binds to hemoglobin, help to carry oxygen from the bloodstream to the cells and plays a role in cellular energy production. While the active heme REV-ERB, and Copp ZnPP inhibit.
"These compounds are as heme, but when you exchange them their functions are different metal centers," said Doug Kojetin, TSRI associate professor who led the study. "This makes us think that the key is the chemistry of the metal ion itself. The modification of the chemistry of this metal center can be a convenient way to target REV-ERB for diabetes and obesity. "
Kojetin and colleagues recently demonstrated that synthetic agonists REV-ERB, as new compounds, reduce body weight in mice that were obese because of the diet.
the first authors of the study, "Structure of REV-ERB_ domain binding ligand bound to a porphyrin Antagonist," is Edna Camacho Matta-McGill University, Montreal and Subhashis Banerjee of the University of Texas Southwestern . Medical Center other authors of the study include Travis S. Hughes and Laura A. Solt of IRST and Yongjun Wang and Thomas P. Burris University School of Medicine St. Louis
work. was supported by the National Institutes of Health (grants DK080201 and DK101871), the biomedical research Program Esther King James and the Florida Department of Health (grant 1KN-09) and the State of Florida.
work can be found here.
About the Scripps research Institute
the Scripps research Institute (TSRI) is one of the most important, independent nonprofit world focusing on research in the biomedical sciences. TSRI is internationally recognized for his contributions to science and health, including its role in the foundation of new treatments for cancer, rheumatoid arthritis, hemophilia, and other diseases. An institution that evolved from the Scripps Metabolic Clinic founded by philanthropist Ellen Browning Scripps in 1924, the institute now employs about 3,000 people at its campus in La Jolla, CA, and Jupiter, FL, where his famous scientists, y including three Nobel prize work toward their next discoveries. The graduate program of the institute, which doctorate degrees in biology and chemistry prices, ranks among the top ten of its kind in the country. For more information, see www.scripps.edu.
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