IHEP OpenIR  > 多学科研究中心
Structural and functional insights into polymorphic enzymes of cytochrome P450 2C8
Jiang, HL; Zhong, FF; Sun, L; Feng, WY; Huang, ZX; Tan, XS; Feng WY(丰伟悦)
2011
发表期刊AMINO ACIDS
卷号40期号:4页码:1195-1204
通讯作者[Jiang, Hualin ; Zhong, Fangfang ; Sun, Lu ; Huang, Zhong-Xian ; Tan, Xiangshi] Fudan Univ, Dept Chem, Shanghai 200433, Peoples R China ; [Jiang, Hualin ; Zhong, Fangfang ; Sun, Lu ; Huang, Zhong-Xian ; Tan, Xiangshi] Fudan Univ, Inst Biomed Sci, Shanghai 200433, Peoples R China ; [Feng, Weiyue] Chinese Acad Sci, Inst High Energy Phys, Beijing 100049, Peoples R China
摘要The cytochrome P450 (CYP) superfamily plays a key role in the oxidative metabolism of a wide range of drugs and exogenous chemicals. CYP2C8 is the principal enzyme responsible for the metabolism of the anti-cancer drug paclitaxel in the human liver. Nearly all previous works about polymorphic variants of CYP2C8 were focused on unpurified proteins, either cells or human liver microsomes; therefore their structure-function relationships were unclear. In this study, two polymorphic enzymes of CYP2C8 (CYP2C8.4 (I264M) and CYP2C8 P404A) were expressed in E. coli and purified. Metabolic activities of paclitaxel by the two purified polymorphic enzymes were observed. The activity of CYP2C8.4 was 25% and CYP2C8 P404A was 30% of that of WT CYP2C8, respectively. Their structure-function relationships were systematically investigated for the first time. Paclitaxel binding ability of CYP2C8.4 increased about two times while CYP2C8 P404A decreased about two times than that of WT CYP2C8. The two polymorphic mutant sites of I264 and P404, located far from active site and substrate binding sites, significantly affect heme and/or substrate binding. This study indicated that two important nonsubstrate recognition site (SRS) residues of CYP2C8 are closely related to heme binding and/or substrate binding. This discovery could be valuable for explaining clinically individual differences in the metabolism of drugs and provides instructed information for individualized medication.
文章类型Article
关键词Structure-function relationship Polymorphism CYP2C8 Drug metabolism Individualized medication
学科领域Biochemistry & Molecular Biology
研究领域[WOS]Biochemistry & Molecular Biology
DOI10.1007/s00726-010-0743-8
URL查看原文
语种英语
WOS类目Biochemistry & Molecular Biology
WOS记录号WOS:000288546700016
引用统计
被引频次:15[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.ihep.ac.cn/handle/311005/239165
专题多学科研究中心
作者单位中国科学院高能物理研究所
推荐引用方式
GB/T 7714
Jiang, HL,Zhong, FF,Sun, L,et al. Structural and functional insights into polymorphic enzymes of cytochrome P450 2C8[J]. AMINO ACIDS,2011,40(4):1195-1204.
APA Jiang, HL.,Zhong, FF.,Sun, L.,Feng, WY.,Huang, ZX.,...&丰伟悦.(2011).Structural and functional insights into polymorphic enzymes of cytochrome P450 2C8.AMINO ACIDS,40(4),1195-1204.
MLA Jiang, HL,et al."Structural and functional insights into polymorphic enzymes of cytochrome P450 2C8".AMINO ACIDS 40.4(2011):1195-1204.
条目包含的文件
文件名称/大小 文献类型 版本类型 开放类型 使用许可
6300.pdf(496KB)期刊论文作者接受稿开放获取CC BY-NC-SA浏览 请求全文
个性服务
推荐该条目
保存到收藏夹
查看访问统计
导出为Endnote文件
谷歌学术
谷歌学术中相似的文章
[Jiang, HL]的文章
[Zhong, FF]的文章
[Sun, L]的文章
百度学术
百度学术中相似的文章
[Jiang, HL]的文章
[Zhong, FF]的文章
[Sun, L]的文章
必应学术
必应学术中相似的文章
[Jiang, HL]的文章
[Zhong, FF]的文章
[Sun, L]的文章
相关权益政策
暂无数据
收藏/分享
文件名: 6300.pdf
格式: Adobe PDF
所有评论 (0)
暂无评论
 

除非特别说明,本系统中所有内容都受版权保护,并保留所有权利。