Many enzymes contain tunnels and gates that are essential to their function. Gates reversibly switch between open and closed conformations and thereby control the traffic of small molecules—substrates, products, ions, and solvent molecules—into and out of the enzyme's structure via molecular tunnels. Many transient tunnels and gates undoubtedly remain to be identified, and their functional roles and utility as potential drug targets have received comparatively little attention. Here, we describe a set of general concepts relating to the structural properties, function, and classification of these interesting structural features. In addition, we highlight the potential of enzyme tunnels and gates as targets for the binding of small molecules. The different types of binding that are possible and the potential pharmacological benefits of such targeting are discussed. Twelve examples of ligands bound to the tunnels and/or gates of clinically relevant enzymes are used to illustrate the different binding modes and to explain some new strategies for drug design. Such strategies could potentially help to overcome some of the problems facing medicinal chemists and lead to the discovery of more effective drugs.

中文翻译：

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酶通道和门作为药物设计中的相关目标

许多酶都包含对其功能至关重要的通道和门。盖茨可逆地在打开和关闭构象之间切换，从而控制小分子（底物，产物，离子和溶剂分子）通过分子通道流入和流出酶的结构。毫无疑问，许多瞬态隧道和大门仍有待确定，它们作为潜在药物靶标的功能和作用受到的关注相对较少。在这里，我们描述了一组与这些有趣的结构特征的结构特性，功能和分类有关的一般概念。此外，我们强调了酶隧道和门作为小分子结合的目标的潜力。讨论了可能的不同类型的结合以及此类靶向的潜在药理学益处。与临床相关酶的通道和/或门结合的配体的十二个例子用于说明不同的结合方式并解释一些新的药物设计策略。这种策略可能有助于克服药物化学家所面临的一些问题，并导致发现更有效的药物。