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Ji?í Jirá?ek Lenka ?áková Emília Antolíková Christopher J. Watson Johan P. Turkenburg Guy G. Dodson Andrzej M. Brzozowski 《Proceedings of the National Academy of Sciences of the United States of America》2010,107(5):1966-1970
Insulin is a key protein hormone that regulates blood glucose levels and, thus, has widespread impact on lipid and protein metabolism. Insulin action is manifested through binding of its monomeric form to the Insulin Receptor (IR). At present, however, our knowledge about the structural behavior of insulin is based upon inactive, multimeric, and storage-like states. The active monomeric structure, when in complex with the receptor, must be different as the residues crucial for the interactions are buried within the multimeric forms. Although the exact nature of the insulin’s induced-fit is unknown, there is strong evidence that the C-terminal part of the B-chain is a dynamic element in insulin activation and receptor binding. Here, we present the design and analysis of highly active (200–500%) insulin analogues that are truncated at residue 26 of the B-chain (B26). They show a structural convergence in the form of a new β-turn at B24-B26. We propose that the key element in insulin’s transition, from an inactive to an active state, may be the formation of the β-turn at B24-B26 associated with a trans to cis isomerisation at the B25-B26 peptide bond. Here, this turn is achieved with N-methylated L-amino acids adjacent to the trans to cis switch at the B25-B26 peptide bond or by the insertion of certain D-amino acids at B26. The resultant conformational changes unmask previously buried amino acids that are implicated in IR binding and provide structural details for new approaches in rational design of ligands effective in combating diabetes. 相似文献
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Oral Diseases (2010) 16 , 242–247 Background: Melatonin is the principal secretory product of the pineal gland. It has immunomodulatory and antioxidant activities, stimulates the proliferation of collagen and osseous tissue and acts as a protector against cellular degeneration associated with aging and toxin exposure. Arising out of its antioxidant actions, melatonin protects against inflammatory processes and cellular damage caused by the toxic derivates of oxygen. As a result of these actions, melatonin may be useful as a co‐adjuvant in the treatment of certain conditions of the oral cavity. Methods: An extensive review of the scientific literature was carried out using PubMed, Science Direct, ISI Web of Knowledge and the Cochrane base. Results: Melatonin, which is released into the saliva, may have important implications for oral diseases. Melatonin may have beneficial effects in certain oral pathologies including periodontal diseases, herpes viral infections and Candida, local inflammatory rocesses, xerostomia, oral ulcers and oral cancer. Conclusions: Melatonin may play a role in protecting the oral cavity from tissue damage caused by oxidative stress. The experimental evidence suggests that melatonin may have utility in the treatment of several common diseases of the oral cavity. However, more specific studies are necessary to extend the therapeutic possibilities to other oral diseases. 相似文献
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Yen-Shan Chen Jeremy Gleaton Yanwu Yang Balamurugan Dhayalan Nelson B. Phillips Yule Liu Laurie Broadwater Mark A. Jarosinski Deepak Chatterjee Michael C. Lawrence Thomas Hattier M. Dodson Michael Michael A. Weiss 《Proceedings of the National Academy of Sciences of the United States of America》2021,118(30)
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The use of prophylactic antibiotics in implant dentistry is controversial. Given the known risks of antibiotic treatment and lack of consensus on using antibiotics at the time of implant insertion, the purpose of this article was to review available studies on use of perioperative prophylactic antibiotics at the time of implant placement and to provide evidence-based recommendations for antibiotic use. The reviewed studies suggest that a single preoperative dose of 2 g amoxicillin 1 hour before implant placement or 1 g amoxicillin 1 hour preoperatively and 500 mg 4 times daily 2 days postoperatively can reduce the rate of implant failure. 相似文献