Identification of Labile Zn Sites in Drug-Target Proteins

被引：17

作者：

Lee, Yu-Ming ^{[1
]}

Wang, Yi-Ting ^{[2
]}

Duh, Yulander ^{[2
]}

Yuan, Hanna S. ^{[2
]}

Lim, Carmay ^{[1
,3
]}

机构：

[1] Acad Sinica, Inst Biomed Sci, Taipei 115, Taiwan

[2] Acad Sinica, Inst Mol Biol, Taipei 115, Taiwan

[3] Natl Tsing Hua Univ, Dept Chem, Hsinchu 300, Taiwan

来源：

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY | 2013年 / 135卷 / 38期

关键词：

ZINC-FINGERS; STRUCTURAL BASIS; DNA RECOGNITION; BREAST-CANCER; BINDING; DOMAIN; INHIBITION; REACTIVITY; MARKER; UHRF1;

D O I：

10.1021/ja406300c

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

Labile Zn fingers (Zfs) in proteins contain Zn-bound thiolates that can react with electrophilic agents, causing Zn2+ ejection and protein unfolding. Such labile Zfs have been shown to be Cys(4) or Cys(3)His cores whose Zn-bound Cys have no hydrogen bonds. Our aim here is to identify labile Zfs in proteins that are promising drug targets using these features. To prove the strategy used, we showed that five proteins with predicted labile Zfs reacted with Zn-ejecting agents, whereas five proteins with no or inert Zfs did not. The comprehensive set of labile Zfs provides new drug targets and guidelines to redesign Zn-ejecting compounds with improved specificity.

引用

收藏

页码：14028 / 14031

页数：4

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