Department of Chemistry and Biochemistry, Price Family Foundation Institute of Structural Biology, University of Oklahoma, Norman, OK 73019, United States.
Department of Chemistry and Biochemistry, Price Family Foundation Institute of Structural Biology, University of Oklahoma, Norman, OK 73019, United States.
Nitric Oxide. 2017 Jul 1;67:26-29. doi: 10.1016/j.niox.2017.04.012. Epub 2017 Apr 24.
N-hydroxyamphetamine (AmphNHOH) is an oxidative metabolite of amphetamine and methamphetamine. It is known to form inhibitory complexes upon binding to heme proteins. However, its interactions with myoglobin (Mb) and hemoglobin (Hb) have not been reported. We demonstrate that the reactions of AmphNHOH with ferric Mb and Hb generate the respective heme-nitrosoamphetamine derivatives characterized by UV-vis spectroscopy. We have determined the X-ray crystal structure of the H64A Mb-nitrosoamphetamine complex to 1.73 Å resolution. The structure reveals the N-binding of the nitroso-d-amphetamine isomer, with no significant H-bonding interactions between the ligand and the distal pocket amino acid residues.
N-羟基苯丙胺（AmphNHOH）是苯丙胺和甲基苯丙胺的氧化代谢物。已知它与血红素蛋白结合后形成抑制性配合物。然而，它与肌红蛋白（Mb）和血红蛋白（Hb）的相互作用尚未报道。我们证明，AmphNHOH 与三价 Mb 和 Hb 的反应生成各自的血红素-亚硝基苯丙胺衍生物，其特征可通过紫外可见光谱来确定。我们已经确定了 H64A Mb-亚硝基苯丙胺复合物的 X 射线晶体结构，分辨率为 1.73Å。该结构揭示了亚硝基-d-苯丙胺异构体的 N 结合，配体与远端口袋氨基酸残基之间没有明显的氢键相互作用。
