4S0Q

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

4S0Q の概要

• エントリーDOI: 10.2210/pdb4s0q/pdb
• 分子名称: Ribonuclease pancreatic, carboplatin (3 entities in total)
• 機能のキーワード: ribonuclease, rna cleavage, hydrolase-rna complex, hydrolase/rna
• 由来する生物種: Bos taurus (bovine,cow,domestic cattle,domestic cow)
• 細胞内の位置: Secreted: P61823
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 28159.15

構造登録者

Merlino, A. (登録日: 2015-01-04, 公開日: 2015-11-18, 最終更新日: 2024-10-16)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.09 Å)