二氢硫辛酰胺脱氢酶的兼职活动：生物技术和生物医学应用,Journal of Molecular Recognition

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二氢硫辛酰胺脱氢酶的兼职活动：生物技术和生物医学应用
Journal of Molecular Recognition ( IF 2.3 ) Pub Date : 2021-06-23 , DOI: 10.1002/jmr.2924
Gideon Fleminger ₁ , Avraham Dayan ₁

Affiliation

二氢硫辛酰胺脱氢酶 (DLDH) 是一种同源二聚体黄素依赖性酶，可催化二氢硫辛酰胺的 NAD ⁺依赖性氧化。该酶是几种多酶复合物的一部分，例如将丙酮酸转化为乙酰辅酶 A 的丙酮酸脱氢酶系统。与其氧化还原活性相伴，DLDH 会产生参与细胞凋亡过程的活性氧 (ROS)。DLDH 具有多种兼职功能。其中之一是粘附到金属氧化物表面的能力。这首先通过在红球菌细胞壁表面上存在的细胞外形式的酶来举例说明. 这种能力在人类、线粒体、DLDH 中是进化保守的并被识别出来。该酶用 Arg-Gly-Asp (RGD) 基团进行了修饰，使其能够与富含整合素的癌细胞相互作用，然后进行“整合素辅助内吞作用”。这允许利用这种酶进行癌症治疗。将 TiO ₂结合特性与 DLDH 的 ROS 产生相结合，使我们能够开发多种医疗应用，包括改善基于 TiO ₂的植入物的骨整合和黑色素瘤的光动力治疗。_二氧化钛在蛋白质分子上与 E3 结合蛋白 (E3BP) 的结合位点重叠的区域鉴定了细菌和人类 DLDH 的结合位点。这种蛋白质对于形成 PDC 的多单元结构至关重要。本综述中描述的 DLDH 的另一个兼职活动是其 DNA 结合能力，可能会影响 DNA 螯合和切碎，从而导致活细胞中的凋亡过程。还讨论了 DLDH 产生的典型 ROS，这与其酶活性及其在癌症和凋亡细胞死亡中的意义有关。

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The moonlighting activities of dihydrolipoamide dehydrogenase: Biotechnological and biomedical applications

Dihydrolipoamide dehydrogenase (DLDH) is a homodimeric flavin-dependent enzyme that catalyzes the NAD⁺-dependent oxidation of dihydrolipoamide. The enzyme is part of several multi-enzyme complexes such as the Pyruvate Dehydrogenase system that transforms pyruvate into acetyl-co-A. Concomitantly with its redox activity, DLDH produces Reactive Oxygen Species (ROS), which are involved in cellular apoptotic processes. DLDH possesses several moonlighting functions. One of these is the capacity to adhere to metal-oxides surfaces. This was first exemplified by the presence of an exocellular form of the enzyme on the cell-wall surface of Rhodococcus ruber. This capability was evolutionarily conserved and identified in the human, mitochondrial, DLDH. The enzyme was modified with Arg-Gly-Asp (RGD) groups, which enabled its interaction with integrin-rich cancer cells followed by “integrin-assisted-endocytosis.” This allowed harnessing the enzyme for cancer therapy. Combining the TiO₂-binding property with DLDH's ROS-production, enabled us to develop several medical applications including improving oesseointegration of TiO₂-based implants and photodynamic treatment for melanoma. The TiO₂-binding sites of both the bacterial and human DLDH's were identified on the proteins' molecules at regions that overlap with the binding site of E3-binding protein (E3BP). This protein is essential in forming the multiunit structure of PDC. Another moonlighting activity of DLDH, which is described in this Review, is its DNA-binding capacity that may affect DNA chelation and shredding leading to apoptotic processes in living cells. The typical ROS-generation by DLDH, which occurs in association with its enzymatic activity and its implications in cancer and apoptotic cell death are also discussed.

更新日期：2021-06-23

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