DTIC ADA436171: Structure and Reactivity of the Phosphotriesterase Active Site PDF
Preview DTIC ADA436171: Structure and Reactivity of the Phosphotriesterase Active Site
ESARETSEIRTOHPSOHP EHT FO YTIVITCAER DNA ERUTCURTS ASCITTIEVE ssuarK sirroM 05802 DM ,ellivkcoR ,ygolonhcetoiB hcraeseR decnavdA retneC TCARTSBA esaretseirtohpsohp detutitsbus latem dna ,tnatum ,evitan eht fo ytivitcaer dna erutcurts ehT ( dyebnimre t)seEidTP ab initio x ehT .snoitaluclac yrtsimehc mutnauq - eht rof erutcurts yar nZ f oegna redi w ahcih wn ieti sevitc atnetepmo cylla-citylata c aotn idegareve ls iemyzn enZ laciteroeht serutcurts nac eb dezimitpo rof latem detutitsbus dnaatum tn evitca .setise hT gnitneserper rof laitnetop evitceffe wen a gnisu deledom si etis evitca eht fo roivaheb larutcurts eht nietorp ralucel otmne m,ncoirtia vt,nsneoorittcaezli er)(aelvoipslu pgenritcaretni nie ht ,ygo l.o nde aohwihTentnoetm lmiumtanHauq ,s) lPsa FainE hte(tneneb etemovgpiatrcfeffe snoitaluclac laciteroeht ekam ot sedoc erutcurts cinortcele fo etius SSEMAG eht ni detnemelpmi ,yp oe ycl ,tsb deioannrvrtoa uitc rtt cagoccsernfuamptireesv trt lysssonydvasenmridn ufho stl ucsiefri c.espmSota we nadn a,stnatu menietsy co teniditsi heti sevitc af oerutcurt seh tn o .detneserp eb lliw ,esalordyh siht rof elihpoelcun eht no lasoporp NOITCUDORTNI This yduts lliw sucof no eht laciteroeht sisylana fo eht evitcaer roivahebf o rohpsohponagro morf esalordyh su Pseudomonasd iminuta hcihw ,)ETP( esaretseirtohpsohp , esaretsenilohclyteca fo srotibihni rehto dna ,namos ,niras ,noxoarap fo sisylordyh eht sezylatac 2][1, no sisahpme hcum htiw deiduts ylevisnetxe neeb sah emyzne sihT . ytivitcaer no tceffe eht snoitatum dna noitutitsbus latem htiw [3 - 8] X . -nZ cillatemib eht fo ,serutcurts yar - nZ [9] dna dC - dC [10] sinahcem dna gnidnib deliated eht gniyduts rof sisab eht edivorp ,semyzne ehT .m erutcurts cinortcele dna cirtemoeg eht morf decuded eb nac msinahcem eht fo stcepsa ralucelom si noitamrofni sihT .etis evitca emyzne eht htiw sexelpmoc etats noitisnart dna tnatcaer eht fo ytrleuvci fs.fe yiroldutlta ctnun irefatmotSibroeplxaena seugo fo tenh atdtncuaoebr ni eht deniatbo neeb evah etis evitca 11][9, gnidnib elbissop eht otni thgisni edivorp serutcurts esehT . we nhti wnev edeugolata cnee beva hsedo mgnidni bll ato ntah ttseggu se w,revewo H.sedom atad gniwohsves lare seitilibissop rof elpmis setartsbus [11] . nevE erom tnatropmie ht tnemegnarra fo sretaw dnuob ni eht evitca etis si ylroo p.doo tsstrneedmneugnarrA foe ht etartsbus ot etartsbus morf tnetsisnoc ton era etis evitca eht ni stneutitsbus la te gninneB gnidael tsum eno“ dna ”gnidnib eht gnirud demrof ylidaer era sexelpmoc evitcudorpnon taht“ tseggus ot gxni snue hnwoitu ahct idweecorp - evit ceamyz n fenogised eer h nteino laat aldarutcur tysar sit[e1s1”] . 1 Report Documentation Page Form Approved OMB No. 0704-0188 Public reporting burden for the collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing the collection of information. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing this burden, to Washington Headquarters Services, Directorate for Information Operations and Reports, 1215 Jefferson Davis Highway, Suite 1204, Arlington VA 22202-4302. Respondents should be aware that notwithstanding any other provision of law, no person shall be subject to a penalty for failing to comply with a collection of information if it does not display a currently valid OMB control number. 1. REPORT DATE 2. REPORT TYPE 3. DATES COVERED 00 JAN 2002 N/A - 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Structure And Reactivity Of The Phosphotriesterase Active Site 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER 5e. TASK NUMBER 5f. WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) 8. PERFORMING ORGANIZATION Center Advanced Research Biotechnology, Rockville, MD 20850 REPORT NUMBER 9. SPONSORING/MONITORING AGENCY NAME(S) AND ADDRESS(ES) 10. SPONSOR/MONITOR’S ACRONYM(S) 11. SPONSOR/MONITOR’S REPORT NUMBER(S) 12. DISTRIBUTION/AVAILABILITY STATEMENT Approved for public release, distribution unlimited 13. SUPPLEMENTARY NOTES This article is from ADA409494 Proceedings of the 2001 ECBC Scientific Conference on Chemical and Biological Defense Research, 6-8 March , Marriott’s Hunt Valley Inn, Hunt Valley, MD. 14. ABSTRACT 15. SUBJECT TERMS 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF 18. NUMBER 19a. NAME OF ABSTRACT OF PAGES RESPONSIBLE PERSON a. REPORT b. ABSTRACT c. THIS PAGE UU 9 unclassified unclassified unclassified Standard Form 298 (Rev. 8-98) Prescribed by ANSI Std Z39-18 e hT larutcurts sisab rof gnidnib si llits ton raelc ecnis eht eerht snoiger deifitnedis a seudiser cillihpordyh dna cibohpordyh htob evah etartsbus eht htiw gnitcaretni 14]13, 12, [9, . d ekorrteodow i ysetnrioalc a drr eieorhtteclean isgnnoeit aethuTm s nieef sz hofaietobsht etartsb ue shhtt isweudis ee r hfstonoitcaret nciire te s hrttoekc ogpnidnib [14] eht ,revewoH . ecnatropmi fo owt seniditsi h,452H( )752H dna nahpotpyr t)131W( ni gnidnib tseggus taht noitcaretni gnidnob negordyh negordyh si 131W ,elpmaxe roF .elbissop osla era s eht- ot dednob etanohpsohp rotibihni ni ehtnZ - nZ emyzne latsyrc erutcurts [9] ees( .)1.gif gniledoMf o ob negordyh eb dluow puorg ortin eht taht swohs osla etis evitca eht otni esanoxoarap ot dedn llehs tsrif eht ni seudiser eht fo snoitatuM .752H [15] eht sdrawot seudiser etis evitca raen ni , nietorp roiretni [7] , dna raen evitca etis seudiser drawot noitulos [6] yfidom ytivitcad na ificeps hg u ssrnodoe ia ahe sgersl.tnslnsoau yli aaaefbcetam thhhehirnoctlTceenotemebd noitanima xfeo eht evitca etis fo ehtnZ - neZ msywz onthe asnhotit aa fncoiibrm eodtcnsa negordyh - .elbaborp era snoitcaretni dednob vresbo latnemirepxE ehT .raf os stnemegnarra gnidnib owt ylno wohs gnidnib eht fo snoita etartsbus si negordyh dednob otdnoces - llehs seudiser dna osla stcaretni htiwn oisrepsid eht ot hcaorppa eht htiw noitac latem eht ot dnib ton seod negyxo lyrohpsohp tub snoitcaretni 2nZ mota ton resol cnaht 4.3 .Å ehT d nt ongcenemised gnsnieabordra dnif leyhrtohpsohp eht sekam 131W fo ecneserp eht ,revewoH .Å 1.2 fo ecnatsid a htiw 2nZ eht ot dnuob negyxo st n. et os ulg teetu n h thicyi 2taaTt ikddnitrsfflnlZwatbofuiudsugibbobsudwuss gest that a .2nZ ot gnidnib tcerid edepmi taht snoitcaretni cirets sah puorg lyhtem a naht regral tneutitsbus ,revewoH eht noitavresbo fo gnidnib ro raen gnidnib ot 2nZd egaruocne ihw 2nZ ot gnidnib yb detaitini sisylordyh eht taht snoitseggus latnemirepxe hc .esaretseirtohpsohp fo etis evitca eht fo citamehcS .1erugiF d ezilibatsed e h t edixordyh gnidnib os ti dluoc tca sa eht elihpoelcun [9] . ,revet wnoeHcer larutcurts atad stseggus taht eht gnidnib fo eht lyrohpsohp negyxo seod tone zilibatsed edixordyh gnidnib [11] . ehT laciteroeht snoitaluclac wohs taht eht tcerid gnidnib foe ht etahpsohp ot rehtie 1nZ ro 2nZ sevael eh tedixordyh sa a gnig d.idrnbagil eW tseggus taht d lee nsltv ourciiietoeawsthbtctaaw fgonidn i.Bed ogmnidn irbeht ineeilihpoelc ue n hstta retaw ot eht evitca etis ni eht ecneserp fo eh tetartsbus si neht trap fo eht ev iettcaaretrsbus 2 .yllaciteroeht ro yllatnemirepxe rehtie deiduts neeb ton sah tub xelpmoc no iltautteiM tssibusk nwon oyy tttriiec vtidilfntaiaccaeps [3, 7] rdanl au c teeulhbotm ot nwonk eb tsum yrtemoeg ralucelom hcihw htiw ycarucca ehT nwonk ton si sisab cinortcele t ehed gri oiuvctstoin ncrn isiupoeirrh tt toscrseel lhaneg aiehhltb asniibatbo yx - latsyr cyar erutcurts [16] sec n.e rfeoffiD a sh twdee frfdonuh na g Åntinza iceerih reftnatiicnagriashc etalymabrac ro etatrapsa eht rehtie ni latem eht ot dnuob etalyxobrac eht fo erutcurts cinortcele tub lareves shtnet fo na Å sia d dec e vi. nn ets riotieeeoaiahnmsftt ciyebueKzholhntoteser e psottcoesf ifreof sn ioesihyttlc oarreo drfgy nh eiettnasoretg sgabu usns oei tteaitlsantasrt deniatbo neeb evah [41,7 ] setartsbus tsom rof taht ecnedive si ereht ,revewoH . ton si etar eht detimil yb eht lacim enhocitcaer [17, 18] . yroehT nac neht etubi rytlntoncacifingis ote ht gnidnatsrednu fo eht msinahcem ta eht ralucelom .level eW evah yltnecer depoleveda rene dna gnidnib eht gnitaluclac rof ygolodohtem htap noitcaer emyzne eht gnola seitreporp citeg tyds nleenelgr itaa uree crdtotpmieecfomotvturoryecrpcflletalstea s claat neelmginriespxe serutcurts tnatum ro detutitsbus latem ot erutcurts [19 - 21] seitreporp citylatac eht otni thgisnI . tr aal le euvdhce et elsnmliioo arm gtfenbhiotd n f ino tboe nitea tahtditt cnssnaaniear retht evitca etis fo eht .emyzne yranimilerP stluser rof esaretseirtohpsohp ydaerla wohst aht od tnemirepxe morf deniatbo htap noitcaer eht dna gnidnib no snoitcuded revoc yletelpmoc ton dC eht fo noitaluclac etaruccA .shtap noitcaer elbissop fo egnar eht - saw erutcurts emyzne dC serutcurts syCXsiH eton siht nI .]02[ esaretseirtohpsohp rof ygolodohtem eht etadilav ot desu ebircsed era etis evitca eht ni stnatum lla rof rof esaretseirtohpsohp ni htap noitcaer cificeps A .d etahpsohplyhtemirt fo gnidnib eht tub detaluclac neeb sah etahpsohplyhtemirt fo sisylordyh eht .ecaps no noitatimil eht ot eud ylfeirb yrev debircsed eb lliw ylno retaw dna DOHTEM Ap p noitacil fo ab initio sdohtem si laitnesse rof et anrouictccaiderp fo eh tseitreporp fo emyzne evitca setis dna rieht elor ni .sisyla thagcuohtlA ab initio mutnauq sdohteme vah deyojne taerg sseccus ni gniziret cnaoriathicsnart setats dna gninimretedtcaer noi shtap in vacuo gnikam smota fo sderdnuh eriuqer nac etis evitca emyzne na fo noitpircsed reporp eht , lla lanoitidart nac ytivitcaer dna gnidnib eht fo erutcip etarucca nA .elbatcartni- sdohtem nortcele ht htiw atad latnemirepxe detimil morf degarevel eb )PFE( slaitnetop tnemgarf evitceffe fo esu e taht ekam n oeihttalu cfloac e ht etnnleibmeanttoocrraiprvtne [22] . eh T, tnnoaittciasenrart ,etats ,rotibihni dna tcudorp ni eht emyzne evitca etis nac won eb dezimitpo htiw ay lluf hc mutnauq eht yb detneserper tnemnorivne nietorp eht htiw noitcaretni eht fo tnemtaert lacime P.Fn E a t ceci nhsihinoige r Tno tiddtPdot ensioeFnrlehinvhmEatihtiotocmtreeeapmglhe ola scitegrene evitaler eht sa llew sa level ralucelom eht no sisylatac fo stcepsa htap noitcaer a gn rof eno fo a egnar fo yllacitylatac tnetepmoc snoitamrofnoc fo eht .nietorpy llacitylataC seirotcejart fo sisylana morf ro erutcurts latsyrc eht morf deniatbo era snoitamrofnoc tnetepmoc noitalumis scimanyd ralucelom a ni [21] eht ro etis evitca eht ni dnuob sretaw fo rebmun ehT . tnemegnarra fo lanretni negordyh sdnob ni eht evitca etis sah neeb dnuof ote ziretcarahc gnidnib retaw rof ecnedive yranimilerP .esatum etamsirohc rof snoitamrofnoc citylatac tnereffid ohpsohp ni ni gnidnib retaw no sdneped ylralimis emyzne siht ni ytivitca taht stseggus esaretseirt x na morf deniatbo era snoitaluclac PFE rof serutcurts laitinI .etis evitca eht - DM ,erutcurts yar ynam ,snoitalumis - scinahcem lacissalc ydob [23] s ro , ime - .yrtsimehc mutnauq laciripme stceffe noitavlos ledom ot dengised saw dohtem laitnetop tnemgarf evitceffe ehT 42[ - ]03 dna si yletairporppa dednetxe ot ebircsed nietorp .snoitcaretni ehT PFE era detnemelpmin i SSEMAG [31] smelborp elucelomoib fo yteirav a ot deilppa neeb yltnecer evah dna 91[ -23 ,12 - 37] . nI e,h dt P oeFlhhEettde omf m oe eveemih tyttdiz cesn,osadesti inn ovoinwiiatdger .nToi g)reSor(ta tdnc noeaai pg)eseAvr(itca lla detaert si noiger A eh - sedulcni dna nortcele 3 yna seudiser taht era yltceri ddevlovni ni eht yrtsimehc ro esohw tnemevom si lacitirco t .sisylatac ehT S ,noiger hcihw secneulfni A hguorht ,citatsortcelenegordyh - ,dednobd na itcaretni cirets ro evisluper detcerid ehT .nainotlimah mutnauq eht ni PFE eht yb deledom si ,sno sdeeid tusilclcii ntbdniaaei tztdsiunorbara itlercohteptslied P FeEdivo repht elvaictocleffe noitca reevtinsi l .uc eepir vteroeiiRtfhtsctcealeid -yte i r rdoaaefvtare nne egee vbsaPhFE fo seudiser nietorp [19] rof dnuof snoitcaretni fo egnar a revo noitcaretni evisluper eht gnittif yb negordyh eht eertraH eht ta deniatbo era PFE llA .etis evitca eht- ni snoitamrofnoc dednob - kcoF ri t ennfheootitaluc l eath c atlohestvel lla dna PFE e -eertraH a yllaitnesse si metsys nortcele - .tnemnorivne nietorp eht fo hcum edulcni nac taht metsys egral yrev a rof noitaluclac kcoF eertraH detcirtser eht ta enod era sehcraes etats noitisnart dna snoitazimitpo yrtemoeg llA - level kcoF SSEMAG ni [31] lla eht tcirtser ot )PCE( laitnetop eroc evitceffe eht gnisu - nortcele snortcele ecnelav eht ot noitaluclac [38,39] lla fo rebmun eht ecniS . ylevitaler -si smota nortcele sisab laitnatsbus a gniriuqer ,egral 300(~ set ,noitcnufeva-w eht fo noitatneserper eht rof )007 4 PEC a ot detcirtser si noitaluclac eht stes sisab deziraloP- .PCE eht ot tnatimocnoc sisab G13 etis evitca latem elgnis a fo erutcurts eht no tceffe laitnatsbus a dah ton evah [40 ,41] larutcurtS . elbanosaer htiw esaretseirtohpsohp rof noitaluclac TFD a htiw derapmoc neeb evah snoitaluclac muimdac yb noitutitsbus cniz gnidulcni serutcurts evitan eht rof tnemeerga ]61[ PFE eht gnisU . latem ezylana ot -na noitutitsbus ydaerla sah esaretseirtohpsohp ni etis evitca eht fo noitanotorp d etarucca devorp [20] . GNIDNIB ETARTSBUS DNA ERUTCURTS ETIS EVITCA llA eht serutcurts rof esaretseirtohpsohp era degarevel morf ehtnZ - nZx - yarl atsyrc erutcurts [9] dC eht rof erutcurts ehT . ehT .snoita-luclac yna etaitini ot desu ton si emyzne dC dC - dC evitca etis erutcurts si detaluclac morf ehtnZ - nZ dna nwohs ot eerga llewh tiw latem rof tnemirepxe rif eht nihtiw selgna sa- llew sa secnatsid dnagil st - llehs ]02[ sedivorp sihT . eno tset fo eht ycaciffe fo eht PFE rof neohittanimre tfeod eht erutcurts fo eht evitca. etis latem eht hguohtlA nZ morf Å 4.0 revo- yb segnahc ecnatsid latem -dC ot nZ - si esaercni eht ,dC yletadneinmioadtebrop yb noitrotsid ni ehttsrif - .llehs ehT lat ssyerrcutcurt swohs taht eht eht ni secnereffid ehT .Å 2.0 nihtiw esopmirepus semyzne dC dna nZ eht fo smota enobkcab in vacuo dna PFE serutcurts era dnuof yliramirp ni eht noitatneiro fo eht sdnagil tahte ra snoc negordyh eht yb deniart eb nac semyzne detutitsbus latem llA .seudiser roiretni- eht ot sdnob nZ eht morf degarevel - .tnemnorivne nietorp PFE eht gnisu nZ e hT evitca etis efsoaretseirtohps oship debircsed ni 1.gif htiw eht nietorpt nemnorivne yltcerid gnicneulfn iehttsrif - .llehs ehTtsrif - llehs stsisnoc fo eht owt latem snoitac dnae ht eseht llA .detalymabrac enisyl eht htiw 961K ,102H ,032H ,75H ,55H ,103D :sdnagil gniwollof lla deredisnoc era seudiser C eht ot kcab s-mota lla gnidulcni nortcele mota ,032H ,esac eno nI . a negordyh enobkcab era ereht ecnis dedulcni si enobkcab edima eht - eht ot snoitcaretni dednob ,452H ,352D ,332D ,232D ,131W era PFE yb eht yb detneserper seudiser ehT .nietorp roiretni ratoms the all If Y309. and F306, M317, L271, H257, erew noitaluclac PFE eht ni detneserpe lla yb detneserper rehtar snoitcnuf sisab 4421 fo latot a eb dluow ereht- ,snoitcnuf sisab nortcele lla deredisnoc eb osla lliw ,131W ,snoitaluclac gnidnib etartsbus eht roF .deriuqer 835 eht naht - ezimitpo dna nortcele noxoarap a fo esac eht nI .etartsbus dnuob eht htiw tcaretni nac ti ecnis d - od sl7,elu5elbao2tlwHaart sebkuisl - eh tesuace bdetanotor pe bo tnesoh cs i452 H.nortcele negordyh fo tnemegnarra tnatropmi eb ot dnuof si 752H- .elbaborp si siht stseggus sdnob eht ni noitceles larihc [14] ni puorg ortin eht ot gnidnob negordyh hguorht snoitcnuf ylbaborp ti tub etanohpsohp eht nehw deledom ylisae si dnob negordyh a hcus ecnis snoxoarap detutitsbus eht psohp nI .noxarap otni detrevnoc si rotibihni cilihpordyh sah nietorp ro roiretni eht ,esaretseirtoh lyl bet hs nsrenoihiifttubirt seigdr aeyhhfcti dhoc mi,hswnoitcare tgnniid nnoebgor ddynha 4 se n ,win eromonrle h rio o ifeedetideiehshgntatrdrhwntraezuaietaadilwstrhrooxtcastelop sepahs nietorp fo nrettap eht fo noitpursiD .sdnib etartsbus eht hcihw otni xob cibohpordyh eht negordyh segnahc yticificeps dna larutcurts rof sisab eht si nietorp eht fo r-oiretni eht otni sdnob t a rhsutn conc ieoethraw ateudmam ni edhnto cde nsda r lidlhnetuhosrhat e evetiitsca [7] . ERUTCURTS TNATUM CXH se reuht Tcfuo ret n slisld nai eotonistit ieanhttisuym cehttsrif - e nteiivs i lteflchoeaths esaretseirtohp seorhap dezimitpo htiw eht áC nezorf rof lla gnidnib .sdnagilA ,h geuhothtl h s cnae4snuabaomcitazimi t epynholitlait irnuif leunsietsyc - ts r ecin hn f ietim5h zotÅrf evitca eht ,llehs nZ a htiw gnidnib dnagil timrep ot ylt-neiciffus strotsid xelpmoc etis - ecnatsid S 2.3about of etsyc eht f-o gnidnib dnagiL .Å 8.2 htob htiw stnatum ruof lla htiw deniatbo saw eni e h,tnoitazimit pdoeniartsnoc n nu na.Ierutcur tdsezimit peo h ntdieniatni asmdnag iglnigdirb deen tidasnlyoylb moatb r 1aynnc leZdlk eaorsn iroiidtbf anneraeht stsCs5e5 Hdn aC75H e,thrsteve w.osHtnatum d 5n e5a.hHeT msi itdtheatsse stesoban n eáaghCcnti vnnoiimar dedivorp era etis evitca eht rof secnatsid dnob tnaveleR .2.gif ni nwohs era ylno serutcurts 75H .1 elbaT ni reted neeb evah noxoarap rof stnatum CXH eht lla fo seitivitca evitaler ehT denim [15] ehT . rellam sahti wevita neh trev odesaercn iytivitc aC75 Helih wytivitc ao nswoh stnatu mC55H taht snoitatum eht fo stceffe larutcurts suoivbo on era erehT .stnatum owt rehto eht ni noitcuder .d ylttucio evwefvihfitTatcaaler se g e tr, veaar1ic hentu odc vZcd,ednaeeo2awfrnofpZhe nZ evitan eht nI .esirprus 1nZ neewteb elbarapmoc si egrahc evitceffe- nidwoL eht ,emyzne nZ ssel si ti tub C032H dna ,C102H ,C75H rof 2nZ naht evitisop erom si 1nZ ,revewoH .2nZ dna evitisop rof55H .C ehT evitceffe segrahc troppus eht noitnetnoc taht 2nZ seod ton yalpa eht ni noxoarap fo noitamrofnoc evitcaer ehT .negyxo lyrohpsohp eht ot gnidnib ni elor citylatac stnat ulm lyi lweblabbmoersp e er rheotrtuitbciuhrn tinsi ehtnZ - e rnuZ thctuirwts on tcerid .snoitac latem eht ot gnidnib lyrohpsohp H55 C H57 C tsrif eht tsuj gniwohs erutcurts tnatum CXH .2 erugiF -.75H .b ,55H .a rof llehs 5 evitca detceleS .1 ELBAT .)Å( CXH rof secnatsid dnob etis H2 30 C H 2 01 C H 5 7 C H 5 5 C nZ -3. 4 3 . 4 5 3 . 6 6 3 . 5 8 Z n 8 1nZ -2 . 0 0 2 . 1 1 2 . 0 3 2 .O 0 a 9 s p 1nZ -2 . 0 5 1 . 9 8 2 . 2 1 1 . 9 1 O H 1nZ -5. 2 0 5 . 7 1 2 . 8 4 2 . 4 7 O l y s 1nZ -5 . 2 0 5 . 7 1 2 . 8 4 2 . 4 7 S 2nZ - 1. 9 1 O H 1 . 9 7 1 . 9 8 1 . 9 0 2nZ -1. 9 8 2 . 0 7 1 . 9 9 1 . 9 7 O l y s 2nZ -2 6 . 4 1 5 . 1 3 S 2 . 3 8 . 3 7 erutcurts tnatum eht ni elor on yalp yehT .snoitaluclac tneserp eht ni PFE era 131W dna 752H dluow yeht os gnidnib noxoarap no tceffe etanidroni na evah dluoc snoitisop rieht ni stfihs tub evah ot eb lla -ortcele n ni yna rehtruf noitaluclac no eht noitcaer .htap ehTe vitcaer snoitamrofnoc htiw dnuob sretaw era deriuqer ot niatbo thgisni otni evitcaer. roivaheb eed sgnet ndit soo isatesiorylaglttbly hgaa metuz 1ahsidnbtme Zrinnatiacpacor tesbnocnU c sihT .nekorb ehT .kcatta cilihpoelcun rof retaw a fo noitavitca eht tsissa neht nac noina lyxobra eh totn ithgisn iedivor po tflest iy btneiciffusn is ierutcurt scinortcel edn alacirtemoe gtnatum .ytivitca ETAHPSOHPLYHTEMIRT DNA RETAW FO GNIDNIB uclaC retaw a ro retaw detagil sdnif esaretseirtohpsohp fo erutcurts etis evitca eht no noital negordyh -tsrif eht ot dednob eht ot noitidda nI .deziralop yrev -si sdnagil cinoi etis evitca llehs aw deziralop siht taht esoporp ew ,erutcurts eht no sah siht stceffe .elihpoelcun eht sa tca nac ret negordyh retaw gnidulcni yB rof moor erom sedivorp siht ,retnec cinoi etis ev-itca eht ot dednob rof detaluclac neeb sah erutcurts a hcuS .retaw eht tceje ot gnivah tuohtiw etartsbus eht gnikcod esaretseirtohpso hhptiw amirt et aehtp as.hoephtspao lrhsytpahslwtbyeuhmstie rnTesohc sa e tdanh a pteess iz r loe iresoehhylehitdptsahw ooart omneeottan sgese rgpleoaphhmtriesp lyhtem puorg si decalper yb eniroulf ro eht etahpsohp negyxo decalper yb a. ruflus etahpsohplyhtemirTorp ylb asbtcae ryre vylwo lescni sereht si on do oggni v.apeulorge hT latem eht ot yltcerid ton tub etis evitca eht ot dnuob dnuof si etahpsohp lyhteirt ]11[ yltnerappA . yna tneutits bruesgral naht eht lyhtem puorg lliw yllaci rtectasretniiw ht eht nahpotpyrtr o eninal atyanheth predrob eht 2nZ .etis fO ,esruoc a tnneeguotlia thlslbiuws tif .ylisae owT serutcurts era dnuof htiw retaw negordyh dednob ot eht gnigdirb edixordyh )a3( roe ht de teanliy sm.ya)lbbr3a( cehT )ePc(nOats iodt eht 1nZo r 2nZ stiu o2b.a2 l y Åhetleiihrwt etis elbissecca tnevlos erom ro 2nZ eht morf Å 4.3 tuoba dnib ot devresbo si etahpsohp [11] . ot dnuob retaW .a ,esaretseirtohpsohp ot retaw dna etahpsohplyhtemirt fo gnidniB .3 erugiF syl detalymabrac .edixordyh gnigdirb ot dnuob retaW .b ,eni 6 tuoba ta detaluclac si tnatcaer evitcaernu ylevitaler siht fo sisylordyh rof ygrene noitavitca ehT 02 ehT.lom/lack noitisnart etats si etal dnatcudorp - ekil sa detseggus yb .tnemirepxee hT lonahtem tcudorp sitbo denia yb naartni - ralucelom notorp refsnart morf eht )P(HO ote ht yxohtem negyxo hcihw si elbarapmoc ot ehtsag - esahp kcatta fo etahpsohplyhtemirty b edixordyh [42] . SNOISULCNOC taht wohs snoitaluclac laciteroehT nZ eht fo erutcurts latsyrc elgnis a esaretsei-rtohpsohp nZ latem eht fo erutcurts etis evitca eht enimreted ot degarevel eb nac dC( emyz-ne detutitsbus - ,)dC sihT .)CXH( seudiser etis evitca fo stnatum dna ,etis evitca eht fo mrof detanotorp ro Hp wol ivorp ro noitcaer eht ot tnaveler serutcurts etis evitca fo egnar ediw a gnicudorp fo snaem a sed gnidnib fgo nsiettsaerrtestbnui s y.lbnaociittaelruocelh atAc wen noit cyaaewrhtap si osla latnemirepxe eht fo sisylana lacitirc dna snoitaluclac eht yb detseggus erehw serutcurts latsyrc negordyh si taht retaw deziralop na htiw detaitini si sisylordyh eht cinoi etis evitca eht- ot dednob htiw etartsbus a taht tseggus setis evitca tnatum dna evitan eht fo erutcurts cinortcelE .seudiser llams stneutitsbus nac dnibe yllauq llew ta rehtie 1nZ ro 2nZ .setis gnidniB fo ehte lpmis ,etahpsohponagro ,etahpsohplyhtemirt ni eht evitca etis stroppus siht .noitnetnoce roM eht ni slatem eht revo dednepsus era tub setis latem eht ta dnib ton lliw setartsbus detacilpmoc tis evitca negordyh retaw a yb kcatta fo ecnatsid ysae nihtiw etahpsohp eht htiw e - eht ni dednob dna nepo yam egdirb enisyl detalymabrac eht tub gnigdirb niamer lliw edixordyh ehT .etis evitca .noitcaer eht ni devlovni eb SECNEREFER .K.V ,igotsaR.1 ,.R.J ,dliW ,.C.T ,gnehC ,.J.J ,knarFeD , Enzymatich ydrolysiso fR ussian - VXb yo rganophosphorush ydrolase. 492 .p :142 .7991 ,.mmoC.seR.syhpoiB.mehcoiB - 6. ,.M.H ,nedloH ,.M.F ,lehsuaR.2 Phosphotriesterase:a ne nzymei ns earcho fi tsn atural substrate. vdA 15 .p :47 .0002 ,.loiB loM saerA taleR lomyznE - 93. ,.M.F ,lehsuaR ,,S.L ,snilluM ,.A.G ,orubmO.3 Structuralc haracterizationo ft hed ivalent cations iteso fb acterialp hosphotriesteraseb y1 13CdN MRs pectroscopy. ,yrtsimehcoiB 1993.3 2:p .4 8 - 55. ,gnoH.4 ,.M.F ,lehsuaR ,.B.S Metal - substratei nteractionsf acilitatet hec atalytica ctivity oft heb acterialp hosphotriesterase. 40901 .p :53 .6991 ,yrtsimehcoiB - 12. ,.M.F ,lehsuaR ,.K.J ,hcolluCcM ,.J.H ,yenohaM ,.M.L ,sniktaW.5 Augmentedh ydrolysiso f diisopropy lf luorophosphatei ne ngineeredm utantso fp hosphotriesterase. ,.mehC.loiB.J 1997:p .2 5596 - 601. ,.M.F ,lehsuaR ,.Y.M ,eahC ,.M.J ,ouK.6 Perturbationst ot hea ctives iteo f phosphotriesterase. 2891 .p :63 .7991 ,yrtsimehcoiB - 8. ,KJ yelsmirG ,.B ,iduoiSiD.7 ,.RJ dliW ,K iaL Modificationo fn eara ctives iter esiduesi n organophosphorush ydrolaser educesm etals toichiometrya nda lterss ubstrates pecificity. 6682 .p :83 .9991 ,yrtsimehcoiB - 72. .R.J ,dliW ,.K.J ,yelsmirG ,.K ,iaL ,.E.C ,relliM ,.D.B ,iduoiSiD.8 , Rationald esigno f 7 organophosphorush ydrolasef ora ltereds ubstrates pecificities. .9991 ,.tcaretnI loiB mehC 119 - 120:p .2 11 - 23. ,.M.H ,nedloH ,.M.F ,lehsuaR ,.M.M ,gninneB ,.L.J ,ekoohnaV.9 Three - dimensional structureo ft hez inc - containingp hosphotrie sterasew itht heb ounds ubstratea nalog diethyl4 - methylbenzylphosphonate. 0206 .p :53 .6991 ,yrtsimehcoiB - 5. ,.MH nedloH ,MF lehsuaR ,MJ ouK ,.M.M ,gninneB.01 Three - dimensionals tructureo ft he binuclearm etalc entero fp hosphotriesterase. 1 ,yrtsimehcoiB 995.3 4:p .7 973 - 8. ,.MH nedloH ,MF lehsuaR ,BS gnoH ,.M.M ,gninneB.11 TheB indingo fS ubstrateA nalogs toP hosphotriesterase. 30556p.J .B2i7o5l2:.0 C0 h0e.m ., - 60. ,.M.F ,lehsuaR , ,.B.S ,gnoH.21 Stereochemicalc onstraintso nt hec atalytich ydrolysiso f o rganophosphaten ervea gentsb yp hosphotriesterase. p. 146: 1999. 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