Shabalin Ivan, Dauter Zbigniew, Jaskolski Mariusz, Minor Wladek, Wlodawer Alexander
Department of Molecular Physiology and Biological Physics, University of Virginia, 1340 Jefferson Park Avenue, Charlottesville, VA 22908, USA.
Synchrotron Radiation Research Section, MCL, National Cancer Institute, Argonne National Laboratory, Argonne, IL 60439, USA.
Acta Crystallogr D Biol Crystallogr. 2015 Sep;71(Pt 9):1965-79. doi: 10.1107/S139900471500629X. Epub 2015 Aug 28.
The anticancer activity of platinum-containing drugs such as cisplatin and carboplatin is considered to primarily arise from their interactions with nucleic acids; nevertheless, these drugs, or the products of their hydrolysis, also bind to proteins, potentially leading to the known side effects of the treatments. Here, over 40 crystal structures deposited in the Protein Data Bank (PDB) of cisplatin and carboplatin complexes of several proteins were analysed. Significant problems of either a crystallographic or a chemical nature were found in most of the presented atomic models and they could be traced to less or more serious deficiencies in the data-collection and refinement procedures. The re-evaluation of these data and models was possible thanks to their mandatory or voluntary deposition in publicly available databases, emphasizing the point that the availability of such data is critical for making structural science reproducible. Based on this analysis of a selected group of macromolecular structures, the importance of deposition of raw diffraction data is stressed and a procedure for depositing, tracking and using re-refined crystallographic models is suggested.
顺铂和卡铂等含铂药物的抗癌活性被认为主要源于它们与核酸的相互作用；然而，这些药物或其水解产物也会与蛋白质结合，这可能导致治疗中出现已知的副作用。在此，对蛋白质数据银行（PDB）中几种蛋白质的顺铂和卡铂复合物的40多个晶体结构进行了分析。在大多数所展示的原子模型中发现了晶体学或化学性质的重大问题，这些问题可追溯到数据收集和精修过程中或多或少的严重缺陷。由于这些数据和模型被强制或自愿存入公开可用的数据库，因此有可能对其进行重新评估，这强调了此类数据的可用性对于使结构科学具有可重复性至关重要这一点。基于对一组选定的大分子结构的分析，强调了原始衍射数据存档的重要性，并提出了一个存档、跟踪和使用重新精修的晶体学模型的程序。
