BACKGROUND We comprehensively analyzed X-ray cocrystal structures of dipeptidyl peptidase IV (DPP-4) and its inhibitor to clarify whether DPP-4 alters its general or partial structure according to the inhibitor used and whether DPP-4 has a common rule for inhibitor binding. RESULTS All the main and side chains in the inhibitor binding area were minimally altered, except for a few side chains, despite binding to inhibitors of various shapes. Some residues (Arg125, Glu205, Glu206, Tyr662 and Asn710) in the area had binding modes to fix a specific atom of inhibitor to a particular spatial position in DPP-4. We found two specific water molecules that were common to 92 DPP-4 structures. The two water molecules were close to many inhibitors, and seemed to play two roles: maintaining the orientation of the Glu205 and Glu206 side chains through a network via the water molecules, and arranging the inhibitor appropriately at the S2 subsite. CONCLUSIONS Our study based on high-quality resources may provide a necessary minimum consensus to help in the discovery of a novel DPP-4 inhibitor that is commercially useful.

中文翻译：

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对二肽基肽酶IV及其抑制剂的共结构的综合分析。

背景技术我们全面分析了二肽基肽酶IV（DPP-4）及其抑制剂的X射线共晶体结构，以阐明DPP-4是否根据使用的抑制剂改变其总体或部分结构，以及DPP-4是否具有抑制剂结合的通用规则。结果抑制剂结合区域中的所有主链和侧链均发生了最小程度的改变，除了少数侧链外，尽管与各种形状的抑制剂结合。该区域中的一些残基（Arg125，Glu205，Glu206，Tyr662和Asn710）具有结合模式，可将抑制剂的特定原子固定在DPP-4中的特定空间位置。我们发现了92个DPP-4结构共有的两个特定水分子。这两个水分子接近许多抑制剂，似乎起着两个作用：经由水分子通过网络保持Glu205和Glu206侧链的取向，并将抑制剂适当地布置在S2亚位点。结论我们基于高质量资源的研究可能提供必要的最低共识，以帮助发现具有商业用途的新型DPP-4抑制剂。