title: Identification of labile Zn sites in drug-target proteins.
abstract: Labile Zn fingers (Zfs) in proteins contain Zn-bound thiolates that can react with electrophilic agents, causing Zn(2+) ejection and protein unfolding. Such labile Zfs have been shown to be Cys4 or Cys3His 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.
authors.affiliation: Institute of Biomedical Sciences and §Institute of Molecular Biology, Academia Sinica, Taipei 115, Taiwan.
authors.forename: Yu-Ming
authors.initials: YM
authors.lastname: Lee
authors.forename: Yi-Ting
authors.initials: YT
authors.lastname: Wang
authors.forename: Yulander
authors.initials: Y
authors.lastname: Duh
authors.forename: Hanna S
authors.initials: HS
authors.lastname: Yuan
authors.forename: Carmay
authors.initials: C
authors.lastname: Lim
mesh_terms: D015082:2,2'-Dipyridyl / Q000031:analogs & derivatives / Q000737:chemistry; D022762:CCAAT-Enhancer-Binding Proteins / Q000737:chemistry; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000737:chemistry; D004220:Disulfides / Q000737:chemistry; D006655:Histone Deacetylases / Q000737:chemistry; D006801:Humans; D011506:Proteins / Q000737:chemistry*; D011994:Recombinant Proteins / Q000737:chemistry; D013438:Sulfhydryl Compounds / Q000737:chemistry; D048029:TNF Receptor-Associated Factor 6 / Q000737:chemistry; D013893:Thiram / Q000737:chemistry; D044767:Ubiquitin-Protein Ligases / Q000737:chemistry; D015032:Zinc / Q000737:chemistry*; D016335:Zinc Fingers
chemical_list: D022762:CCAAT-Enhancer-Binding Proteins; D004220:Disulfides; D011506:Proteins; D011994:Recombinant Proteins; D013438:Sulfhydryl Compounds; D048029:TNF Receptor-Associated Factor 6; D013893:Thiram; C001105:2,2'-dipyridyl disulfide; D015082:2,2'-Dipyridyl; C412484:DNMT3L protein, human; D004248:DNA (Cytosine-5-)-Methyltransferases; C485369:RCHY1 protein, human; C406364:UHRF1 protein, human; D044767:Ubiquitin-Protein Ligases; C492634:PHF21A protein, human; D006655:Histone Deacetylases; D015032:Zinc