petsko1992_comment_on_MiltonHIVprot

petsko1992_comment_on_MiltonHIVprot - posedsolelyofRNA. The...

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Unformatted text preview: posedsolelyofRNA. The recognitionof furthercatalyticversatilityinRNA justifies considerationofitsinvolvement inother earlybiochemistry.Recently,invitroselec- tionand amplificationmethods (7) have openedthewaytotheexplorationofnew RNA functions,withouttheconstraintsof biology. Over the coming yearswe may expecttoseeevenfurtherexpansionofthe catalyticcapacityofRNA. Almost 25 yearsagomy colleague, Prof. DagmarRinge,wasaskedduringherPh.D. thesisdefense tospeculateon what would happenifa proteolyticenzyme(onethatcuts the peptidestrandofaprotein)couldbemade fromallD-aminoacidsinsteadofthenaturally occurringL-enantiomers.She repliedthatthe protein wouldprobablyfoldproperlyandhave full catalyticactivity,butonlyagainstpeptide substratesofthesamechirality.Herexamin- ersdidnotbelieveher (shepassedanyway), butnow, aquarterofacenturylater,the experimenthasbeendoneandthatis exactly whathappens.StephenKentandhisassoci- atesattheScrippsResearchInstitutehave achievedthetotalchemical synthesisofan all-D-aminoacidenzyme, theacidprotease from the human immunodeficiency virus (HIV).As reportedinthisissueofScience(1), theprotein displaysa chiralspecificityfor both substrates and inhibitors that is the opposite ofthatshownbythenaturallyoccur- ringall-L-aminoacidenzyme. "Chiral" comesfromtheGreekwordfor "hand,"andtheterm"handedness" is often used interchangeablytodescribethesame property.An object is chiralif itcannotbe superimposed onitsmirrorimage bysimple rotationsandtranslations.The quintessential exampleoftwoobjectsofoppositechirality are the leftand right human hands (see figure).Two objectsofoppositehandedness can alwaysinteractwiththe same achiral object:forexample,boththeleft and right handscanholdabaseballinthesameway. But theirinteractions with another chiral object mustbe different,andin some cases onlyoneofthemmaybeableto interactat all.You cannot use a left-handedbaseball gloveonyour righthand.(Anotherexample: Two righthands canshakewitheach other, ascantwolefthands.Theleftand right hands canalso clasp,but onemusttum upside down TheauthorisattheRosenstielBasicMedicalSciences Research Center,DepartmentsofBiochemistryand Chemistry,BrandeisUniversity,Waltham, MA 02254. REFERENCES 1.H.F.Noller,V.Hoffarth,L.Zimniak, Science,256, 1416(1992). 2. J.A.Piccirilli,T.S.McConnell,A.J.Zaug, H.F. Noller,T.R.Cech,ibid.,p.1420. 3. H.F.Noller,Annu.Rev.Biochem.60,191 (1991). 4. C.R.Woese, Microbiol.Rev.51,221 (1987). 5. T.R.Cech,Science236, 1532(1987). 6. C.R.Woese, TheGeneticCode: TheMolecular BasisforGeneExpression(HarperandRow,New York,1967),p.186. 7. J.Abelson, Science249,488 (1990). todoso.)Moleculesarechiraliftheylacka center,plane,oraxisofsymmetry. Ifthey haveanyoneofthese,theywillbe superim- posableontheirmirrorimages....
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petsko1992_comment_on_MiltonHIVprot - posedsolelyofRNA. The...

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