Lysyl oxidase-like 2 (LOXL2) is a copper-dependent amine oxidase that catalyzes the oxidative deamination of the ε-amino group of lysines/hydroxylysines on substrate proteins (collagen and elastin) to form aldehyde groups. The generated aldehyde groups are of significance in crosslinking with the adjacent aldehyde or ε-amino group on proteins in extracellular matrix. In this paper, we have studied the reaction mechanism of LOXL2 by means of quantum mechanics (QM) and combined QM and molecular mechanics (QM/MM) methods. This study is divided into two parts, i.e. the biosynthesis of lysine tyrosylquinone (LTQ) cofactor and oxidative deamination of ε-amino group of lysine by LTQ. For the former part, the reaction is driven by a large exothermicity of about 284 kJ/mol. Dopaquinone radical (DPQr) is suggested to be an intermediate state in this reaction. In addition, His652 residue is predicted to serve as proton acceptor. The rate-determining step for the biosynthesis of LTQ is found to be hydrogen-atom abstraction from the benzene ring on substrate by Cu²⁺-hydroxide, which is a proton-coupled electron transfer (PCET) process with an energy barrier of 84 kJ/mol. For the latter part, the reaction is exothermic by about 145 kJ/mol, and the copper ion is proposed to play a role of redox catalyst in the last step to generate the product of aldehyde. However, the copper ion might not be indispensable for the latter part, which is consistent with the previous study.

类赖氨酸氧化酶2（LOXL2）是一种铜依赖性胺氧化酶，可催化底物蛋白（胶原蛋白和弹性蛋白）上赖氨酸/羟基赖氨酸的ε-氨基的氧化脱氨基反应形成醛基。产生的醛基在与细胞外基质中蛋白质上的相邻醛或ε-氨基交联中具有重要意义。在本文中，我们通过量子力学（QM）以及结合量子力学和分子力学（QM / MM）的方法研究了LOXL2的反应机理。这项研究分为两个部分，即赖氨酸酪氨酸醌（LTQ）辅因子的生物合成和赖氨酸的ε-氨基被LTQ氧化脱氨基。对于前一部分，该反应由约284 kJ / mol的大放热驱动。多巴醌自由基（DPQr）被认为是该反应的中间状态。另外，His652残基预计将用作质子受体。发现用于LTQ的生物合成的决定速率的步骤是通过Cu从底物上的苯环提取氢原子^2+-氢氧化物，是质子耦合电子转移（PCET）过程，能垒为84 kJ / mol。对于后一部分，反应放热约145 kJ / mol，并且建议铜离子在最后一步产生醛产物的过程中起氧化还原催化剂的作用。但是，铜离子对于后半部分可能不是必不可少的，这与先前的研究一致。