Crystallographic Studies of Chemokines, Chemokine Receptors, and Related Protein

最重要的成就之一是显示了人防御素5（HD 5）对乳头瘤病毒的强抑制特性。这些特性使HD 5成为预防乳头瘤病毒感染的局部药物的潜在候选者。今年，我们还发表了关于三种人类α-defensis，HNP 4，HD 5和HD 6的第一个结构数据。这一成就使所有人类α-防御素的结构特征。在另一项研究中，我们发表了人类β-防御素分子中表位的初步草案，该表位负责结合和/或激活趋化因子受体CCR 6。在这一努力的继续，whcih是接近完成，我们确定了更多的细节β-防御素的结构决定因素，whcih是必要的生产性相互作用与CCR 6。我们还表明，这些蛋白质之一，hBD 4，不激活CCR 6，并详细解释了这种缺陷的原因。与Lu博士合作，我们研究了人类α-防御素化学的另外两个方面：其序列中Arg的高比例（与Lys相比），β-防御素未观察到的现象，以及前肽形式的前区对人类α-防御素折叠效率的影响。在这两种情况下，我们提供了一个合理化，基于结构研究。

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.