利什曼病是由利什曼原虫属动质体寄生虫引起的一系列被忽视的热带疾病。目前的化学疗法受到严重限制，对新的抗利什曼药的需求具有紧迫的国际重要性。布罗莫结构域是表观遗传阅读器结构域，已显示出用于癌症治疗的有希望的治疗潜力，并且也可能成为治疗寄生虫病的有吸引力的靶点。在这里，我们研究杜氏利什曼原虫溴结构域因子 5 (LdBDF5) 作为抗利什曼病药物发现的靶标。 LdBDF5 在 N 端串联重复中包含一对溴结构域（BD5.1 和 BD5.2）。我们纯化了杜氏乳杆菌 BDF5 的重组溴结构域，并通过 X 射线晶体学确定了 BD5.2 的结构。使用组蛋白肽微阵列和荧光偏振测定，我们鉴定了 LdBDF5 溴结构域与源自组蛋白 H2B 和 H4 的乙酰化肽的结合相互作用。在包括热位移测定、荧光偏振和 NMR 在内的正交生物物理测定中，我们表明 BDF5 溴结构域与人溴结构域抑制剂 SGC-CBP30、溴孢菌素和 I-BRD9 结合；此外，SGC-CBP30 在细胞活力测定中表现出针对利什曼原虫前鞭毛体的活性。这些发现例证了 BDF5 作为利什曼原虫可能的药物靶点的潜力，并为未来开发针对这种表观遗传读取蛋白的优化抗利什曼原虫化合物奠定了基础。

Leishmaniases are a collection of neglected tropical diseases caused by kinetoplastid parasites in the genus Leishmania. Current chemotherapies are severely limited, and the need for new antileishmanials is of pressing international importance. Bromodomains are epigenetic reader domains that have shown promising therapeutic potential for cancer therapy and may also present an attractive target to treat parasitic diseases. Here, we investigate Leishmania donovani bromodomain factor 5 (LdBDF5) as a target for antileishmanial drug discovery. LdBDF5 contains a pair of bromodomains (BD5.1 and BD5.2) in an N-terminal tandem repeat. We purified recombinant bromodomains of L. donovani BDF5 and determined the structure of BD5.2 by X-ray crystallography. Using a histone peptide microarray and fluorescence polarization assay, we identified binding interactions of LdBDF5 bromodomains with acetylated peptides derived from histones H2B and H4. In orthogonal biophysical assays including thermal shift assays, fluorescence polarization, and NMR, we showed that BDF5 bromodomains bind to human bromodomain inhibitors SGC-CBP30, bromosporine, and I-BRD9; moreover, SGC-CBP30 exhibited activity against Leishmania promastigotes in cell viability assays. These findings exemplify the potential BDF5 holds as a possible drug target in Leishmania and provide a foundation for the future development of optimized antileishmanial compounds targeting this epigenetic reader protein.