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

Shabalin, I.G.; Dauter, Zbigniew; Jaskólski, Mariusz; Minor, Władek; Wlodawer, Alexander

doi:10.1107/s139900471500629x

Cited by 57 publications

(73 citation statements)

References 63 publications

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“…In a recent report by Shabalin et al 20 it was pointed out that the crystallographic data of the Atox1 dimer by Boal and Rosenzweig (PDB code 3IWX) could also be interpreted on the basis of full occupancy of the tetrahedral cavity by Cu + instead of a {Pt(NH 3 ) 2 2+ } occupancy of only 0.4.…”

Section: ■ Introductionmentioning

confidence: 96%

Oxaliplatin Binding to Human Copper Chaperone Atox1 and Protein Dimerization

et al. 2016

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Copper trafficking proteins have been implicated in the cellular response to platinum anticancer drugs. We investigated the reaction of the chaperone Atox1 with an activated form of oxaliplatin, the third platinum drug to reach worldwide approval. Unlike cisplatin, which contains monodentate ammines, oxaliplatin contains chelated 1,2-diaminocyclohexane (DACH), which is more resistant to displacement by nucleophiles. In solution, one or two {Pt(DACH)(2+)} moieties bind to the conserved CXXC metal-binding motif of Atox1; in the latter case the two sulfur atoms likely bridging the two platinum units. At longer reaction times, a dimeric species is formed whose composition, Atox12·Pt(2+)2, indicates complete loss of the diamine ligands. Such a dimerization process is accompanied by partial unfolding of the protein. Crystallization experiments aiming at the characterization of the monomeric species have afforded, instead, a dimeric species resembling that already obtained by Boal and Rosenzweig in a similar reaction performed with cisplatin. However, while in the latter case there was only one Pt-binding site (0.4 occupancy) made of four sulfur atoms of the CXXC motifs of the two Atox1 chains in a tetrahedral arrangement, we found, in addition, a secondary Pt-binding site involving Cys41 of the B chain (0.25 occupancy). Moreover, both platinum atoms have lost their diamines. Thus, there appears to be little relationship between what is observed in solution and what is formed in the solid state. Since full occupancy of the tetrahedral cavity is a common feature of all Atox1 dimeric structures obtained with other metal ions (Cu(+), Cd(2+), and Hg(2+)), we propose that in the case of platinum, where the occupancy is only 0.4, the remaining cavities are occupied by Cu(+) ions. Experimental evidence is reported in support of the latter hypothesis. Our proposal represents a meeting point between the initial proposal of Boal and Rosenzweig (0.4 Pt occupancy) and the reinterpretation of the original crystallographic data put forward by Shabalin et al. (1 Cu occupancy), and could apply to other cases.

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Section: ■ Introductionmentioning

confidence: 96%

Oxaliplatin Binding to Human Copper Chaperone Atox1 and Protein Dimerization

et al. 2016

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“…The EDS is used internally by COOT [39, 40], PyMOL [41] and other programs to download ready-to-view electron density maps for inspection. As with many servers that reach the end of an initial funding period, this server is still available and running in an automatic mode, but it is no longer supported or developed, and there is no mechanism to correct errors, despite its widespread usefulness and appreciation [42]. …”

Section: Structural Biology Data Resourcesmentioning

confidence: 99%

Databases, Repositories, and Other Data Resources in Structural Biology

Zheng

Porebski

Grabowski

et al. 2017

Methods in Molecular Biology

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Structural biology, like many other areas of modern science, produces an enormous amount of primary, derived, and “meta” data with a high demand on data storage and manipulations. Primary data comes from various steps of sample preparation, diffraction experiments, and functional studies. These data are not only used to obtain tangible results, like macromolecular structural models, but also to enrich and guide our analysis and interpretation of existing biomedical studies. Herein we define several categories of data resources, (a) Archives, (b) Repositories, (c) “Databases” and (d) Advanced Information Systems, that can accommodate primary, derived, or reference data. Data resources may be used either as web portals or internally by structural biology software. To be useful, each resource must be maintained, curated, and be integrated with other resources. Ideally, the system of interconnected resources should evolve toward comprehensive “hubs” or Advanced Information Systems. Such systems, encompassing the PDB and UniProt, are indispensable not only for structural biology, but for many related fields of science. The categories of data resources described herein are applicable well beyond our usual scientific endeavors.

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“…The availability of raw diffraction images for subsequent reprocessing could lead to the extraction of additional usable data, enable some previously deposited structures to be improved and/or permit a better interpretation of biomedical results (Shabalin et al, 2015;Sato et al, 2006;Ramachandraiah et al, 2002). In general, raw diffraction images of macromolecular crystals are discarded owing to disk-space limitations or are lost owing to the obsolescence of digital storage media.…”

Section: Introductionmentioning

confidence: 99%

“…The requirement to deposit this intermediate data is now regarded as one of the most important advances in archiving structural information and ensuring robust validation and reproducibility of the method and results (Terwilliger & Bricogne, 2014). In some cases, access to structure-factor amplitudes has enabled structures to be reinterpreted (Shabalin et al, 2015;Raaijmakers & Romã o, 2006;Choi et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

“…Improperly defined ligands may lead to wasted efforts in both academic and commercial research. Re-refinement cannot extend back to the diffraction experiment, but must rely on the deposited structure factors; for this reason, full reprocessing of the diffraction data may be necessary to successfully reinterpret the macromolecular structure (Shabalin et al, 2015;Ramachandraiah et al, 2002;Sato et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

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A public database of macromolecular diffraction experiments

Grabowski

Langner

Cymborowski

et al. 2016

Acta Crystallogr D Struct Biol

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109

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The low reproducibility of published experimental results in many scientific disciplines has recently garnered negative attention in scientific journals and the general media. Public transparency, including the availability of `raw' experimental data, will help to address growing concerns regarding scientific integrity. Macromolecular X-ray crystallography has led the way in requiring the public dissemination of atomic coordinates and a wealth of experimental data, making the field one of the most reproducible in the biological sciences. However, there remains no mandate for public disclosure of the original diffraction data. The Integrated Resource for Reproducibility in Macromolecular Crystallography (IRRMC) has been developed to archive raw data from diffraction experiments and, equally importantly, to provide related metadata. Currently, the database of our resource contains data from 2920 macromolecular diffraction experiments (5767 data sets), accounting for around 3% of all depositions in the Protein Data Bank (PDB), with their corresponding partially curated metadata. IRRMC utilizes distributed storage implemented using a federated architecture of many independent storage servers, which provides both scalability and sustainability. The resource, which is accessibleviathe web portal at http://www.proteindiffraction.org, can be searched using various criteria. All data are available for unrestricted access and download. The resource serves as a proof of concept and demonstrates the feasibility of archiving raw diffraction data and associated metadata from X-ray crystallographic studies of biological macromolecules. The goal is to expand this resource and include data sets that failed to yield X-ray structures in order to facilitate collaborative efforts that will improve protein structure-determination methods and to ensure the availability of `orphan' data left behind for various reasons by individual investigators and/or extinct structural genomics projects.

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

Cited by 57 publications

References 63 publications

Oxaliplatin Binding to Human Copper Chaperone Atox1 and Protein Dimerization

Oxaliplatin Binding to Human Copper Chaperone Atox1 and Protein Dimerization

Databases, Repositories, and Other Data Resources in Structural Biology

A public database of macromolecular diffraction experiments

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