《Modeling Steroid 5alpha-reductase and Characterizing Its Potential Active Sites Modeling Steroid 5alpha-reductase and Characterizing Its Potential Active Sites》.pdfVIP

3l卷 11期 结 构 化 学 (JIEGOUHUAXUE) Vo1．31．No．11 2012 11 Chinese Struct． C l6l8—1626 M odelingSteroid5alpha--reductaseand CharacterizingItsPotentialActiveSites① ouMin．．Rui LIJun．．Qian~ (CollegeofChemistryandChemicalEngineering,FuzhouUniversity,Fuzhou350002，China) ABSTRACT Steroid5alpha．reductaseofhumanisanenzymeinthebiosyntheticpathwayfrom testosterone(T)todihydrotestosterone(DHT)．Uptonow,nocrystalstructureofthisenzymehas beenreported．However,knowledgeofthetertiarystructureandpossibleactivesitesisessentialfor understandingthecatalysismechanism andforthedesignofinhibitors．Amodelwithputativeactive siteshas been created and evaluated by using homology modeling and moleculardocking techniquesbasedon thebioinformaticsknowledge．Thehomologymodelisoptimized in Swiss PDB Viewerwith MM method andsubstratestructuresbeforedocking arealsooptimized on HF／6—31G TheactivesiteofrthedockingofNADP’T’DHTandFinasterideis1ocatednearthe N．terminusofenzyme．Fouractiveamino acidsintheactivesiteareidentifiedasAla26，Arg53， Arg176 and Lys177．Reaction procedure，binding paUern ofactive sites，the typesofweak interactionandsoonarealsodiscussed． Keywords：5alpha-reductase，homologymodeling，benignprostatichyperplasia 1 INTRoDUCTIoN jsoofrm jsthepredominantenzyme in sebaceous glandsand liver,whereasthe type IIenzyme is Steroid5alpha—reductase(S5AR)1samembrane— dominantintl1eprostate．5alpha—Reductasehasbeen bound，NADPH ·dependentenzymethatirreversibly shown tobeinvolvedinhuman disorders．such as catalyzesthereduction of4-ene-·3·O·XO-·steroidsto bening prostatichyperplasia(BPH)，alopecia，acne thecorresp