Department of Chemistry, University of Toledo, Toledo, Ohio 34606, USA.
Med Res Rev. 2010 Mar;30(2):290-326. doi: 10.1002/med.20190.
Drug-resistant forms of Mycobacterium tuberculosis (M. tuberculosis) are increasing worldwide, underscoring the need to develop new drugs to treat the disease. One of the factors that make tuberculosis difficult to treat is the unique architecture of the mycobacterial cell wall. In this review, we catalogue the enzymes involved in the synthesis of the mycolylarabinogalactan (mAG), a key structural component of the mycobacterial cell wall. In addition, we review the enzymes required for the synthesis of the related lipoarabinomannan (LAM), a structure that possesses immunomodulatory properties. The integrity of the mAG and LAM is critical to the viability of mycobacteria, and many of the established antimycobacterial agents target enzymes critical to the synthesis of the mAG and LAM. Recently, new enzymes catalyzing synthetic steps in the synthesis of the mAG and LAM have been characterized and their substrate specificity determined. In this report, we review recent efforts to characterize the enzymes involved in mAG and LAM synthesis and describe the compounds used to inhibit the enzymes or characterize their catalytic activity.
耐药形式的结核分枝杆菌（结核分枝杆菌）在世界范围内不断增加，这突显出需要开发新的药物来治疗这种疾病。使结核病难以治疗的因素之一是分枝杆菌细胞壁的独特结构。在这篇综述中，我们列出了参与合成分枝菌酸阿拉伯半乳聚糖（mAG）的酶，这是分枝杆菌细胞壁的关键结构成分。此外，我们还回顾了合成相关脂阿拉伯甘露聚糖（LAM）所需的酶，LAM 是一种具有免疫调节特性的结构。mAG 和 LAM 的完整性对分枝杆菌的生存能力至关重要，许多已建立的抗分枝杆菌药物都针对合成 mAG 和 LAM 的关键酶。最近，已鉴定出催化 mAG 和 LAM 合成中合成步骤的新酶，并确定了它们的底物特异性。在本报告中，我们回顾了最近在鉴定参与 mAG 和 LAM 合成的酶方面的努力，并描述了用于抑制这些酶或表征其催化活性的化合物。
