维生素B6依赖转移酶酶（PDXK）是由PDXK基因编码的一种维生素B6依赖型转移酶酶，对白血病细胞的增殖至关重要。其活性受到干扰会导致代谢异常和核苷酸和多胺水平降低。PDXK和吡哆醛5'-磷酸（PLP）在各种癌瘤中高表达，使它们成为抗癌药物设计的有望靶标。针对PDXK可能作为癌症治疗的治疗方法具有潜力。本研究旨在发现可能有选择性地中断吡哆醛磷酸（PLP）与吡哆醛激酶（PDXK）结合的潜在抑制剂。采用分子对接方法对含有7,28,747种天然及药物类化合物的商业库进行虚拟筛选，以靶向PDXK的底物结合口袋。发现了六个有前途的抑制剂，并对PDXK-配体复合物进行了全原子分子动力学模拟100 ns，以评估其结合构象的稳定性。模拟结果显示，ZINC095099376、ZINC01612996、ZINC049841390、ZINC095098959、ZINC01482077和ZINC03830976的结合引起了轻微的结构变化并稳定了PDXK的结构。该分析提供了有关参与PDXK-PLP复合物形成的关键残基的宝贵信息，并可用于设计特异性和有效的PDXK抑制剂。根据本研究，这些化合物可以作为抗癌剂开发，并以PDXK作为进一步研究的潜在候选物。由Ramaswamy H. Sarma传达。

Pyridoxal kinase (PDXK) is a vitamin B6-dependent transferase enzyme encoded by the PDXK gene, crucial for leukemic cell proliferation. Disruption of its activity causes altered metabolism and reduced levels of nucleotides and polyamines. PDXK and pyridoxal 5'-phosphate (PLP) are overexpressed in various carcinomas, making them promising targets for drug design against cancer. Targeting PDXK may hold promise as a therapeutic approach for cancer treatment. This study focused on discovering potential inhibitors that could selectively interrupt the binding of pyridoxal phosphate (PLP) to pyridoxal kinase (PDXK). A commercially available library of 7,28,747 natural and druglike compounds was virtually screened using a molecular docking approach to target the substrate binding pocket of PDXK. Six promising inhibitors were identified, and all-atom molecular dynamics simulations were conducted on the PDXK-ligand complexes for 100 ns to assess their binding conformational stability. The simulation results indicated that the binding of ZINC095099376, ZINC01612996, ZINC049841390, ZINC095098959, ZINC01482077, and ZINC03830976 induced a slight structural change and stabilized the PDXK structure. This analysis provided valuable information about the critical residues involved in the PDXK-PLP complex formation and can be utilized in designing specific and effective PDXK inhibitors. According to this study, these compounds could be developed as anticancer agents targeting PDXK as a potential candidate for further study.Communicated by Ramaswamy H. Sarma.