Koch Kerstin, Chen Yuxing, Feng Joy Y, Borroto-Esoda Katyna, Deville-Bonne Dominique, Gallois-Montbrun Sarah, Janin Joël, Moréra Solange
Yeast Structural Genomics, IBBMC UMR 8619 CNRS, Universite Paris-Sud, Orsay, France.
Nucleosides Nucleotides Nucleic Acids. 2009 Aug;28(8):776-92. doi: 10.1080/15257770903155899.
Tenofovir is an acyclic phosphonate analog of deoxyadenylate used in AIDS and hepatitis B therapy. We find that tenofovir diphosphate, its active form, can be produced by human nucleoside diphosphate kinase (NDPK), but with low efficiency, and that creatine kinase is significantly more active. The 1.65 A x-ray structure of NDPK in complex with tenofovir mono- and diphosphate shows that the analogs bind at the same site as natural nucleotides, but in a different conformation, and make only a subset of the Van der Waals and polar interactions made by natural substrates, consistent with their comparatively low affinity for the enzyme.
替诺福韦是一种用于艾滋病和乙肝治疗的无环膦酸酯类脱氧腺苷类似物。我们发现，其活性形式替诺福韦二磷酸可由人核苷二磷酸激酶（NDPK）产生，但效率较低，且肌酸激酶的活性明显更高。NDPK与替诺福韦单磷酸和二磷酸复合物的1.65埃X射线结构表明，这些类似物与天然核苷酸结合于同一位点，但构象不同，且仅形成天然底物所形成的范德华力和极性相互作用的一部分，这与其对该酶的相对低亲和力一致。
