College of Pharmacy and Health Sciences, Texas Southern University, Houston, TX 77004, USA.
Tuberculosis (Edinb). 2009 Dec;89 Suppl 1:S55-9. doi: 10.1016/S1472-9792(09)70013-7.
The discovery of anti-tuberculosis agents that target new pathways is crucial for effective short-term TB therapy that will limit the development of resistance. The clinical significance of multidrug-resistant and extensively drug-resistant strains of Mycobacterium tuberculosis, latent TB and Human Immunodeficiency Virus co-infection in tuberculosis patients have made the development of new antimycobacterials more imperative. A better understanding of the major pathways that are involved in the pathogenesis, survival, and dormancy of Mtb will aid in the identification of new drug targets. Here, we review the N-terminal methionine excision (NME) pathway as a potential drug target during host infection with M. tuberculosis. The removal of the N-terminal methionine is a requirement for some proteins prior to post-translational modifications and processing. Therefore, an understanding of the physiological relevance of the two families of enzymes at the center of NME - peptide deformylases and methionine aminopeptidases - has the prospect of adding novel targets and antimycobacterials to the pipeline.
发现针对新途径的抗结核药物对于有效的短期结核病治疗至关重要，这将限制耐药性的发展。耐多药和广泛耐药结核分枝杆菌菌株、潜伏性结核病和人类免疫缺陷病毒合并感染在结核病患者中的临床意义，使得开发新的抗分枝杆菌药物变得更加紧迫。更好地了解参与 Mtb 发病机制、存活和休眠的主要途径将有助于确定新的药物靶点。在这里，我们回顾 N-末端甲硫氨酸切除（NME）途径作为宿主感染结核分枝杆菌时的一个潜在药物靶点。在翻译后修饰和加工之前，某些蛋白质需要去除 N-末端甲硫氨酸。因此，了解 NME 中心的两种酶家族——肽脱甲酰酶和甲硫氨酸氨肽酶——的生理相关性有望为药物研发管线增添新的靶点和抗分枝杆菌药物。
