4S18

The X-ray structure of the adduct formed in the reaction between bovine pancreatic ribonuclease and oxaliplatin

Summary for 4S18

• Entry DOI: 10.2210/pdb4s18/pdb
• Related: 4OT4 4S0Q
• Descriptor: Ribonuclease pancreatic, CYCLOHEXANE-1(R),2(R)-DIAMINE-PLATINUM(II) (3 entities in total)
• Functional Keywords: ribonuclease fold, cleavage of rna, rna, bovine pancreas, hydrolase
• Biological source: Bos taurus (bovine,cow,domestic cattle,domestic cow)
• Cellular location: Secreted: P61823
• Total number of polymer chains: 2
• Total formula weight: 29272.25

Authors

Merlino, A. (deposition date: 2015-01-09, release date: 2015-11-25, Last modification date: 2024-10-16)

Primary citation

Messori, L.,Marzo, T.,Merlino, A.
Interactions of carboplatin and oxaliplatin with proteins: Insights from X-ray structures and mass spectrometry studies of their ribonuclease A adducts.
J.Inorg.Biochem., 153:136-142, 2015

PubMed 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.

PubMed: 26239545
DOI: 10.1016/j.jinorgbio.2015.07.011

Experimental method

X-RAY DIFFRACTION (2.27 Å)