Mycobacterium tuberculosis KasA as a drug target: Structure-based inhibitor design.
Mycobacterium tuberculosis KasA as a drug target: Structure-based inhibitor design.
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DOI：
10.3389/fcimb.2022.1008213
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发表时间：
2022
影响因子：
5.7
通讯作者：
中科院分区：
文献类型：
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作者：
最近的研究报道了β-酮酰基酰基载体蛋白KasA作为结核分枝杆菌的可药物靶点。本文综述了主要类型的KasA抑制剂的现状，重点介绍了基于结构的设计方法的重要贡献，这些方法利用了KasA单独或与抑制剂复合的x射线晶体结构。讨论了每个抑制剂类别中解决的问题，同时详细介绍了与KasA的特征相互作用和构效关系。对这些发现的批判性分析应该为新的KasA抑制剂研究结核分枝杆菌的基本生物学奠定基础，并形成具有抗药敏和耐药感染活性的具有临床意义的新抗结核分子的基础。
Recent studies have reported the β-ketoacyl-acyl carrier protein KasA as a druggable target for Mycobacterium tuberculosis. This review summarizes the current status of major classes of KasA inhibitors with an emphasis on significant contributions from structure-based design methods leveraging X-ray crystal structures of KasA alone and in complex with inhibitors. The issues addressed within each inhibitor class are discussed while detailing the characterized interactions with KasA and structure-activity relationships. A critical analysis of these findings should lay the foundation for new KasA inhibitors to study the basic biology of M. tuberculosis and to form the basis of new antitubercular molecules of clinical significance with activity against drug-sensitive and drug-resistant infections.