Viars Shane, Valentine Jason, Hernick Marcy
Department of Pharmaceutical Sciences, Appalachian College of Pharmacy, Oakwood, VA 24631, USA.
Biomolecules. 2014 May 16;4(2):527-45. doi: 10.3390/biom4020527.
The LmbE-like superfamily is comprised of a series of enzymes that use a single catalytic metal ion to catalyze the hydrolysis of various substrates. These substrates are often key metabolites for eukaryotes and prokaryotes, which makes the LmbE-like enzymes important targets for drug development. Herein we review the structure and function of the LmbE-like proteins identified to date. While this is the newest superfamily of metallohydrolases, a growing number of functionally interesting proteins from this superfamily have been characterized. Available crystal structures of LmbE-like proteins reveal a Rossmann fold similar to lactate dehydrogenase, which represented a novel fold for (zinc) metallohydrolases at the time the initial structure was solved. The structural diversity of the N-acetylglucosamine containing substrates affords functional diversity for the LmbE-like enzyme superfamily. The majority of enzymes identified to date are metal-dependent deacetylases that catalyze the hydrolysis of a N-acetylglucosamine moiety on substrate using a combination of amino acid side chains and a single bound metal ion, predominantly zinc. The catalytic zinc is coordinated to proteins via His2-Asp-solvent binding site. Additionally, studies indicate that protein dynamics play important roles in regulating access to the active site and facilitating catalysis for at least two members of this protein superfamily.
类LmbE超家族由一系列利用单个催化金属离子催化各种底物水解的酶组成。这些底物通常是真核生物和原核生物的关键代谢物，这使得类LmbE酶成为药物开发的重要靶点。在此，我们综述了迄今为止已鉴定的类LmbE蛋白的结构和功能。虽然这是金属水解酶的最新超家族，但该超家族中越来越多具有功能意义的蛋白已得到表征。类LmbE蛋白的现有晶体结构揭示了一种类似于乳酸脱氢酶的罗斯曼折叠，在最初的结构被解析时，这代表了（锌）金属水解酶的一种新折叠。含N - 乙酰葡糖胺底物的结构多样性为类LmbE酶超家族提供了功能多样性。迄今为止鉴定出的大多数酶是金属依赖性脱乙酰酶，它们利用氨基酸侧链和单个结合金属离子（主要是锌）的组合催化底物上N - 乙酰葡糖胺部分的水解。催化锌通过His2 - Asp - 溶剂结合位点与蛋白质配位。此外，研究表明蛋白质动力学在调节活性位点的可及性以及促进该蛋白超家族至少两个成员的催化作用中发挥重要作用。
