软物质与功能材料(刘向阳) 3

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1、Outline•Introduction:Proteinsandthestructuredetermination•Proteincrystallization:challengesandtechniquesIntroduction:ImportanceofproteincrystallizationStructureofprotein(3D):StructuralbiologyanddrugdesignControlleddrugdelivery:bioavailabilityBioseparation:recrystallizationX-rayCrystallography1Int

2、roduction:StructuralbiologyanddrugdesignDoyouknow…?•>100Kdifferentproteinsinlivingorganisms,builtby~20aminoacids.Eachwithuniquestructureandbio-functionality.•Knownstructure:onlylessthan1KproteinsIntroduction:Proteins•Proteinseitherachieveallofthecellstructureandfunctionsortheymakealloftheothermolecu

3、lesandstructureswhichgivefunctionstocells.•Almostallyourcells,includingskin,hair,andmusclesareallmadeofproteins.2Introduction:TypeofProteins•Globularprotein▫Enzyme…▫Transport…▫Storage…▫Defense…antibody▫…•Membraneprotein▫Signal…▫Transport…Introduction:TypeofProteins•Fibrilprotein▫Structural…▫…Protein

4、Subunits:TheAminoAcids3ProteinSubunits:TheAminoAcidsEachaminoacidhasacentralcarbonatom(thecarbon)towhichvariousfunctionalgroupsareattachedAminoCarboxylicacidgroupAllofthemhavebasicallythesamestructureexceptforwhatoccursattheVariablesidechainRplaceholderRdefiningdifferentaminoacids.StructuralFormu

5、lasforthe20AminoAcids4Biologicallyimportantmolecules-protein:LevelsofStructurePrimary:Literally,thesequenceofaminoacidsAstringofbeads(upto20differentcolors)Secondary:ThewaytheaminoacidchaincoilsorfoldsDescribingthewayaknotistiedTertiary:Overallthree-dimensionalshapeofapolypeptideDescribingw

6、hataknotlookslikefromtheoutsideQuaternary:ConsistsofmorethanonepolypeptideLikeseveralcompletedknotsgluedtogether5Whyproteincrystallization?Howtodeterminethe4levelsofstructuresofproteins?•X-raydiffraction:highresolution,largeproteins•NuclearMagneticResonance(NMR):insolutions,lowresolutionKeystages

7、intheproteinstructuredeterminationX-raydiffraction1.Toobtainhighqualitycrystals2.Toobtainthediffractionwithsufficientsize(monthsoryears)pattern(1~2days)3.Toobtainthemolecularstructurebysolvethediffrac