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首页> 外文期刊>Journal of Molecular Biology >The Bowman-Birk inhibitor reactive site loop sequence represents anindependent structural beta-hairpin motif
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The Bowman-Birk inhibitor reactive site loop sequence represents anindependent structural beta-hairpin motif

机译：Bowman-Birk抑制剂反应位点环序列代表独立的结构性β-发夹基序

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摘要

We have determined the NMR structure in aqueous solution of a dis disulphide-cyclised 11-residue peptide that forms a stable beta -hairpin, incorporating a type VIb beta -turn. The structure is found to be extremely well ordered for a short peptide, with the 30 lowest energy simulated annealing structures having an average pairwise r.m.s. deviation of only 0.36 Angstrom over the backbone. AU but three side-chains adopt distinct conformations, allowing a detailed analysis of their involvement in cross-strand interactions. The peptide sequence analysed originates from a previously reported study, which identified potent inhibitors of human leukocyte elastase from screening a combinatorial peptide library based on the short protein beta -sheet segment that forms the reactive site loop of Bowman-Birk inhibitors. A detailed comparison of the peptide's solution structure with the corresponding region in the whole protein structure reveals a very good correspondence not only for the backbone (r.m.s. deviation approximate to0.7 Angstrom) but also for the side-chains. This isolated beta -hairpin retains the biologically active "canonical conformation" typical of small serine proteinase inhibitor proteins, which explains why it retains inhibitory activity. Since the structural integrity is sequence-inherent and does not depend upon the presence of the remaining protein, this beta -hairpin represents an independent structural motif and so provides a useful model of this type of protein architecture and its relation to biological function. The relationship between the conformation of this beta -hairpin and its biological activity is discussed.
机译：我们已经确定了二硫键环化的11-残基肽在水溶液中的NMR结构，该肽形成了稳定的β-发夹，并结合了VIb型β-转角。发现该结构对于短肽来说是非常有序的，具有30种最低能量的模拟退火结构具有平均成对的r.m.s。主干上的偏差仅为0.36埃。非盟但三个侧链采用截然不同的构象，从而允许对其跨链相互作用的参与进行详细分析。分析的肽序列源自先前报道的一项研究，该研究通过基于形成鲍曼-伯克抑制剂的反应性位点环的短蛋白β-折叠片段筛选组合肽文库，鉴定了人类白细胞弹性蛋白酶的有效抑制剂。对该肽的溶液结构与整个蛋白质结构中相应区域的详细比较显示，不仅对于主链（r.m.s.偏差接近0.7埃）而且对于侧链都有非常好的对应关系。这种分离的β-发夹蛋白保留了小的丝氨酸蛋白酶抑制剂蛋白典型的生物活性“规范构象”，这解释了为什么它保留了抑制活性。由于结构完整性是序列固有的，并且不依赖于剩余蛋白质的存在，因此该β-发夹代表了独立的结构基序，因此为此类蛋白质结构及其与生物学功能的关系提供了有用的模型。讨论了该β-发夹的构象与其生物学活性之间的关系。

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