4S18: The X-ray Structure Of The Adduct Formed In The Reaction Between Bovine Pancreatic Ribonuclease And Oxaliplatin

Citation:
Abstract
Oxaliplatin and carboplatin are two platinum(II) drugs in widespread clinical use for the treatment of various types of cancers; yet, structural information on their interactions with proteins is scarce. Here, the X-ray structures of the adducts formed upon reaction of carboplatin and oxaliplatin with bovine pancreatic ribonuclease (RNase A) are reported and compared with results obtained for the structure of the RNase A-cisplatin adduct derived from isomorphous crystals, under the same experimental conditions. Additional details on the binding mode of these metallodrugs toward RNase A are provided by electrospray ionization mass spectrometry (ESI MS) measurements, thus offering insight on the occurring metal-protein interactions. Notably, while carboplatin and cisplatin mainly bind the side chain of Met29, oxaliplatin also binds the side chains of Asp14, of catalytically important His119 and, to a lesser extent, of His105. On the basis of the available data, a likely mechanism for oxaliplatin hydrolysis and binding to the protein is proposed. These results are potentially useful for a better understanding of the biological chemistry, toxicity and side effects of this important class of antitumor agents.
PDB ID: 4S18Download
MMDB ID: 134355
PDB Deposition Date: 2015/1/9
Updated in MMDB: 2015/12
Experimental Method:
x-ray diffraction
Resolution: 2.27  Å
Source Organism:
Similar Structures:
Biological Unit for 4S18: monomeric; determined by author and by software (PISA)
Molecular Components in 4S18
Label Count Molecule
Protein (1 molecule)
1
Ribonuclease Pancreatic(Gene symbol: RNASE1)
Molecule annotation
Chemicals (3 molecules)
1
3
* Click molecule labels to explore molecular sequence information.

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