Erhardt Stefan, Jaime Elke, Weston Jennie
Institute of Organic and Macromolecular Chemistry, Friedrich Schiller University, Humboldtstrasse 10, D-07743 Jena, Germany.
J Am Chem Soc. 2005 Mar 23;127(11):3654-5. doi: 10.1021/ja042797q.
Nature has provided the binuclear zinc based active site of bovine lens leucine aminopeptidase (blLAP) with two water channels: one for substrate docking and a much smaller one (function unknown) above Zn1. In addition, Zn1 possesses an unusual pentacoordinate geometry with a loosely bound carbonyl ligand (Ala333). Extensive DFT calculations on a model of the active site provide first mechanistic implications for these structural features. The weakly bound carbonyl ligand is capable of functioning as a "traffic cop" to direct water molecules coming from the small channel into the heart of the active site. A water sluice is thus generated that is capable of repeatedly providing a series of nucleophilic active "Zn-OH" functionalities.
自然界赋予牛晶状体亮氨酸氨肽酶（blLAP）的双核锌活性位点两个水通道：一个用于底物对接，另一个在Zn1上方，尺寸小得多（功能未知）。此外，Zn1具有不寻常的五配位几何结构，带有一个松散结合的羰基配体（Ala333）。对活性位点模型进行的广泛密度泛函理论（DFT）计算为这些结构特征提供了初步的机理启示。弱结合的羰基配体能够充当“交通警察”，将来自小通道的水分子引导到活性位点的核心。由此产生了一个水闸，能够反复提供一系列亲核活性的“Zn-OH”官能团。
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