Mitić Nataša, Miraula Manfredi, Selleck Christopher, Hadler Kieran S, Uribe Elena, Pedroso Marcelo M, Schenk Gerhard
Department of Chemistry, National University of Ireland, Maynooth, Maynooth, Co. Kildare, Ireland.
Department of Chemistry, National University of Ireland, Maynooth, Maynooth, Co. Kildare, Ireland; School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Queensland, Australia.
Adv Protein Chem Struct Biol. 2014;97:49-81. doi: 10.1016/bs.apcsb.2014.07.002. Epub 2014 Nov 4.
At least one-third of enzymes contain metal ions as cofactors necessary for a diverse range of catalytic activities. In the case of polymetallic enzymes (i.e., two or more metal ions involved in catalysis), the presence of two (or more) closely spaced metal ions gives an additional advantage in terms of (i) charge delocalisation, (ii) smaller activation barriers, (iii) the ability to bind larger substrates, (iv) enhanced electrostatic activation of substrates, and (v) decreased transition-state energies. Among this group of proteins, enzymes that catalyze the hydrolysis of ester and amide bonds form a very prominent family, the metallohydrolases. These enzymes are involved in a multitude of biological functions, and an increasing number of them gain attention for translational research in medicine and biotechnology. Their functional versatility and catalytic proficiency are largely due to the presence of metal ions in their active sites. In this chapter, we thus discuss and compare the reaction mechanisms of several closely related enzymes with a view to highlighting the functional diversity bestowed upon them by their metal ion cofactors.
至少三分之一的酶含有金属离子作为多种催化活性所必需的辅因子。对于多金属酶（即参与催化的两个或更多金属离子）而言，两个（或更多）紧密间隔的金属离子的存在在以下方面具有额外优势：（i）电荷离域，（ii）较小的活化能垒，（iii）结合更大底物的能力，（iv）增强底物的静电活化，以及（v）降低过渡态能量。在这组蛋白质中，催化酯键和酰胺键水解的酶形成了一个非常突出的家族，即金属水解酶。这些酶参与多种生物学功能，并且越来越多的金属水解酶在医学和生物技术的转化研究中受到关注。它们的功能多样性和催化效率很大程度上归因于其活性位点中金属离子的存在。因此，在本章中，我们将讨论并比较几种密切相关的酶的反应机制，以突出其金属离子辅因子赋予它们的功能多样性。
