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.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Intramural Research (Z01)
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National Cancer Institute Division of Clinical Sciences
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Wu, Zhibin; Li, Xiangqun; Ericksen, Bryan et al. (2007) Impact of pro segments on the folding and function of human neutrophil alpha-defensins. J Mol Biol 368:537-49
Zou, Guozhang; de Leeuw, Erik; Li, Chong et al. (2007) Toward understanding the cationicity of defensins. Arg and Lys versus their noncoded analogs. J Biol Chem 282:19653-65
Pazgier, M; Hoover, D M; Yang, D et al. (2006) Human beta-defensins. Cell Mol Life Sci 63:1294-313
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Pazgier, Marzena; Lubkowski, Jacek (2006) Expression and purification of recombinant human alpha-defensins in Escherichia coli. Protein Expr Purif 49:1-8
Xie, Cao; Prahl, Adam; Ericksen, Bryan et al. (2005) Reconstruction of the conserved beta-bulge in mammalian defensins using D-amino acids. J Biol Chem 280:32921-9
Economopoulou, Matina; Bdeir, Khalil; Cines, Douglas B et al. (2005) Inhibition of pathologic retinal neovascularization by alpha-defensins. Blood 106:3831-8
Wu, Zhibin; Cocchi, Fiorenza; Gentles, David et al. (2005) Human neutrophil alpha-defensin 4 inhibits HIV-1 infection in vitro. FEBS Lett 579:162-6
Wu, Z; Ericksen, B; Tucker, K et al. (2004) Synthesis and characterization of human alpha-defensins 4-6. J Pept Res 64:118-25
Szyk, Agnieszka; Lu, Wuyuan; Xu, Chenqi et al. (2004) Structure of the scorpion toxin BmBKTtx1 solved from single wavelength anomalous scattering of sulfur. J Struct Biol 145:289-94

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