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Crystallography and chemistry should always go together: a cautionary tale of protein complexes with cisplatin and carboplatin

DOI: 10.1107/S139900471500629X DOI Help
PMID: 26327386 PMID Help

Authors: Ivan Shabalin (University of Virginia) , Zbigniew Dauter (Argonne National Laboratory) , Mariusz Jaskolski (Adam Mickiewicz University in PoznaƄ) , Wladek Minor (University of Virginia) , Alexander Wlodawer (National Cancer Institute)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Acta Crystallographica Section D Biological Crystallography , VOL 71 , PAGES 1965 - 1979

State: Published (Approved)
Published: September 2015

Abstract: 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.

Journal Keywords: Cisplatin;Carboplatin;Crystal Structure;Error Corrections;Structural Databases;Structure Re-Refinement;Validation;Data Reprocessing;Reproducibility

Subject Areas: Biology and Bio-materials

Instruments: I04-Macromolecular Crystallography