Seeonlineversionforlegendandreferences.PartIappearedintheSeptember18issue.212Cell139,October2,2009©2009ElsevierInc.DOI10.1016/j.cell.2009.08.009SnapShot:AntibioticInhibitionofProteinSynthesisIIDanielSohmen,1JoergM.Harms,2FrankSchlünzen,3andDanielN.Wilson1,41UniversityofMunich,Germany;2MPSD,UniversityofHamburg,Germany;3DESY,Hamburg,Germany;4CiPS-M,Munich,Germany212.e1Cell139,October2,2009©2009ElsevierInc.DOI10.1016/j.cell.2009.08.009SnapShot:AntibioticInhibitionofProteinSynthesisIIDanielSohmen,1JoergM.Harms,2FrankSchlünzen,3andDanielN.Wilson1,41UniversityofMunich,Germany;2MPSD,UniversityofHamburg,Germany;3DESY,Hamburg,Germany;4CiPS-M,Munich,GermanyThetranslationalapparatusisoneofthemajortargetsforantibioticsinthebacterialcell.Antibioticspredominantlyinteractwiththefunctionalcentersoftheribosome,namelythemessengerRNA(mRNA)-transferRNA(tRNA)decodingregiononthe30Ssubunit,thepeptidyltransferasecenteronthe50Ssubunit,ortheribosomalexittunnelthroughwhichthenascentpolypeptidechainpassesduringtranslation.Proteinsynthesiscanbedividedintothreephases:initiation,elongation,andtermination/recycling.1.InitiationTranslationinitiationoperatesthrougha30Sinitiationcomplex(30S-IC),consistingofthe30S,mRNA,initiatorfMet-tRNA,andthreeinitiationfactors,IF1,IF2,andIF3.Sub-sequently,the30S-ICassociateswiththe50S,whichreleasestheinitiationfactors(IFs)andleavestheinitiator-tRNAatthepeptidyl-tRNA-bindingsite(Psite),base-pairedtothestartcodonofthemRNA.Theantibioticsedeine,GE81112,andkasugamycininterferewith30S-ICassembly,whereasformationofafunctional70S-ICisblockedbytheorthosomycinsandpactamycins.2.ElongationTheelongationphaseinvolvesthemovementoftRNAsinacyclicfashionthroughthethreetRNA-bindingsites(A→P→E)ontheribosome.Thefirststepinthecycleinvolvesthedeliveryoftheaminoacyl-tRNA(aa-tRNA)totheaa-tRNA-bindingsite(Asite),whichisfacilitatedbytheelongationfactorEF-Tu•GTP.HydrolysisofGTPbyEF-Tuleadstoitsdissociationfromtheribosome,allowingaa-tRNAaccommodation.Peptide-bondformationthenproceeds...
