Z01 SC 010386 (Z01) | |||
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Title | Crystallographic Studies of Chemokines, Chemokine Receptors, and Related Proteins | ||
Institution | NCI, Bethesda, MD | ||
Principal Investigator | Lubkowski, Jacek | NCI Program Director | N/A |
Cancer Activity | N/A | Division | CCR |
Funded Amount | $181,517 | Project Dates | 10/01/2002 - N/A |
Fiscal Year | 2007 | Project Type | Intramural |
Research Topics w/ Percent Relevance | Cancer Types w/ Percent Relevance | ||
Arthritis (10.0%) Autoimmune Diseases (50.0%) Digestive Diseases (10.0%) |
Colon/Rectum (10.0%) Lung (20.0%) |
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Research Type | |||
Normal Functioning Systemic Therapies - Discovery and Development |
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Abstract | |||
One of the most significant accomplishments was to show a strong inhibitory properties of human defensin 5 (HD5) against the papillomaviruses. These properties make HD5 a potential candidate for the topical agent in preventing the papillomavirus infection. This year we also published the first structural data on three human alpha-defensis, HNP4, HD5, and HD6. This accomplishments makes all human alpha-defensins structurally characterized. In the other study, we published the preliminary draft of the epitope in the human beta-defensin molecules, that is responsible for binding and/or activating the chemokine receptor, CCR6. In continuation of this effort, whcih is near-complete, we identified more details on the structural determinants of beta-defensins, whcih are necessary for productive interaction with CCR6. We also showed that one of these proteins, hBD4, does not activate CCR6 and explained, in detail, the reason for this defficiency. In collaboration with Dr. Lu, we studies two other aspects of human alpha-defensins' chemistry: high ratio of Arg (as compared to Lys) in their sequences, the phenomenon not observed for beta-defensins, and effect of the pro-region, in a pro-peptide form, for the folding efficiency of human alpha-defensins. In both cases, we provided a rationalization, based largery on structural studies. |