Organometallic ruthenium anticancer complexes inhibit human glutathione-S-transferase pi

doi:10.1016/j.jinorgbio.2013.07.029

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	Organometallic ruthenium anticancer complexes inhibit human glutathione-S-transferase pi
	Lin, Yu 1,2; Huang, Yongdong 3; Zheng, Wei 1,2; Wang, Fuyi 1,2; Habtemariam, Abraha 4; Luo, Qun 1,2; Li, Xianchan 1,2; Wu, Kui 1,2; Sadler, Peter J.4; Xiong, Shaoxiang 1,2
刊名	JOURNAL OF INORGANIC BIOCHEMISTRY
	2013-11-01
卷号	128 页码:77-84
关键词	Organometallic Ruthenium Complex Anticancer Glutathione-s-transferase Enzyme Inhibition Mass Spectrometry
ISSN号	0162-0134
DOI	10.1016/j.jinorgbio.2013.07.029
英文摘要	The organometallic ruthenium(II) anticancer complexes [(eta(6)-arene)Ru(en)Cl](+) (arene = p-cymene (1), biphenyl (2) or 9,10-dihydrophenanthrene (3); en = ethylenediamine), exhibit in vitro and in vivo anticancer activities. In the present work, we show that they inhibit human glutathione-S-transferase pi (GST pi) with IC50 values of 59.4 +/- 13, 63.2 +/- 0.4 and 37.2 +/- 1.1 mu M, respectively. Mass spectrometry revealed that complex 1 binds to the S-donors of Cys15, Cys48 within the G-site and Cys102 at the interface of the GST pi dimer, while complex 2 binds to Cys48 and Met92 at the dimer interface and complex 3 to Cys15, Cys48 and Met92. Moreover, the binding of complex 1 to Cys15 and Cys102, complex 2 to Cys48 and complex 3 to Cys15 induces the irreversible oxidation of the coordinated thiolates to sulfenates. Molecular modeling studies indicate that the coordination of the {(arene)Ru(en)}(2+) fragment to Cys48 blocks the hydrophilic G-site sterically, perhaps preventing substrate from proper positioning and accounting for the reduction in enzymatic activity of ruthenated GST pi. The binding of the ruthenium arene complexes to Cys102 or Met92 disrupts the dimer interface which is an essential structural feature for the proper functioning of GMT, perhaps also contributing to the inhibition of GST pi. (C) 2013 Elsevier Inc. All rights reserved.
语种	英语
出版者	ELSEVIER SCIENCE INC
WOS记录号	WOS:000326060800009
内容类型	期刊论文
源URL	[http://ir.iccas.ac.cn/handle/121111/53689]
专题	中国科学院化学研究所
通讯作者	Wang, Fuyi
作者单位	1.Beijing Natl Lab Mol Sci, Beijing 100190, Peoples R China 2.Chinese Acad Sci, Inst Chem, CAS Key Lab Analyt Chem Living Biosyst, Beijing 100864, Peoples R China 3.Chinese Acad Sci, Inst Proc Engn, Natl Key Lab Biochem Engn, Beijing 100190, Peoples R China 4.Univ Warwick, Dept Chem, Coventry CV4 7AL, W Midlands, England
推荐引用方式 GB/T 7714	Lin, Yu,Huang, Yongdong,Zheng, Wei,et al. Organometallic ruthenium anticancer complexes inhibit human glutathione-S-transferase pi[J]. JOURNAL OF INORGANIC BIOCHEMISTRY,2013,128:77-84.
APA	Lin, Yu.,Huang, Yongdong.,Zheng, Wei.,Wang, Fuyi.,Habtemariam, Abraha.,...&Xiong, Shaoxiang.(2013).Organometallic ruthenium anticancer complexes inhibit human glutathione-S-transferase pi.JOURNAL OF INORGANIC BIOCHEMISTRY,128,77-84.
MLA	Lin, Yu,et al."Organometallic ruthenium anticancer complexes inhibit human glutathione-S-transferase pi".JOURNAL OF INORGANIC BIOCHEMISTRY 128(2013):77-84.