Crystallographic studies of chemokine receptors and their ligands

最重要的成就之一是显示出强烈的抑制特性 人防御素5（HD 5）对乳头状瘤病毒。这些特性使HD 5成为一种潜在的 预防乳头瘤病毒感染的局部药物的候选物。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 这些成就使所有人类α-防御素的结构特征化。在另一 在这项研究中，我们发表了人类β-防御素分子中表位的初步草案， 负责结合和/或激活趋化因子受体CCR 6。在 继续这项工作，whcih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，这是必要的生产相互作用， CCR 6。我们还表明，这些蛋白质之一，hBD 4，不激活CCR 6，并解释说， 详细地说，这一缺陷的原因。与卢博士合作，我们研究了另外两个 人α-防御素的化学方面：在它们的化学组成中Arg（与Lys相比）的高比率， 序列，β-防御素未观察到的现象，以及前区的作用，在一个 前肽形式，用于人α-防御素的折叠效率。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.