Medicinal Mushroom Research Group (MMRG), Department of Molecular Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
Department of Oral Biology and Biomedical Sciences, MAHSA University, Selangor, Malaysia.
Comput Biol Chem. 2022 Feb;96:107620. doi: 10.1016/j.compbiolchem.2021.107620. Epub 2021 Dec 23.
Angiotensin-converting enzyme (ACE) regulates blood pressure and has been implicated in several conditions including lung injury, fibrosis and Alzheimer's disease. Medicinal mushroom Ganordema lucidum (Reishi) cystathionine beta-synthase (GlCBS) was previously reported to possess ACE inhibitory activities. However, the inhibitory mechanism of CBS protein remains unreported. Therefore, this study integrates in silico sequencing, structural and functional based-analysis, protein modelling, molecular docking and binding affinity calculation to elucidate the inhibitory mechanism of GlCBS and Lignosus rhinocerus (Tiger milk mushroom) CBS protein (LrCBS) towards ACE. In silico analysis indicates that CBSs from both mushrooms share high similarities in terms of physical properties, structural properties and domain distribution. Protein-protein docking analysis revealed that both GlCBS and LrCBS potentially modulate the C-terminal domain of ACE (C-ACE) activity via regulation of chloride activation and/or prevention of substrate entry. GICBS and LrCBS were also shown to interact with ACE at the same region that presumably inhibits the function of ACE.
血管紧张素转换酶（ACE）调节血压，与多种疾病有关，包括肺损伤、纤维化和阿尔茨海默病。药用蘑菇灵芝（Ganoderma lucidum）半胱氨酸β-合酶（GlCBS）先前被报道具有 ACE 抑制活性。然而，CBS 蛋白的抑制机制尚未报道。因此，本研究整合了基于序列、结构和功能的分析、蛋白质建模、分子对接和结合亲和力计算，以阐明 GlCBS 和 Lignosus rhinocerus（虎奶菇）CBS 蛋白（LrCBS）对 ACE 的抑制机制。 计算机分析表明，两种蘑菇的 CBS 在物理性质、结构性质和结构域分布方面具有高度相似性。蛋白-蛋白对接分析表明，GlCBS 和 LrCBS 都可能通过调节氯激活和/或阻止底物进入来调节 ACE 的 C 末端结构域（C-ACE）活性。GICBS 和 LrCBS 还被证明与 ACE 在同一区域相互作用，该区域可能抑制 ACE 的功能。
