1. Protein Chemistry and Protein Engineering 서울대학교 화학생물공학부 백 승 렬

2. Potential Creative Researchers Understanding Multidisciplinary Subject Leaders with Vision for the Future

3. 단백질 공학 : 단백질의 변형을 통하여 유용성이 뛰어난 신기능성 단백질의 생산 유전공학 : 생물공학의 제 1 의 물결 [ 다량의 단백질 제공 ] 단백질공학 : 생물공학의 제 2 의 물결 [ 산업적 효용가치 증대 ] 따라서, 생명과학 관련 다양한 분야의 지식과 기술의 접목 필요성

4. Central Dogma

6. Cycle of Protein Engineering

7. 돌연변이 유도 : [1] rational design: site-directed mutagenesis [2] non-rational (random) design: DNA shuffling or directed evolution Structure-Function Relationship of Protein 단백질의 변형을 통하여 다양한 성질의 변화를 추구함. Examples [1] 산업적 효소 : protease, glucose isomerase, calf chymosin, papain, amylase, cellulase 및 xylanase, pectinolytic enzyme, lipase 등 [2] 의료용 단백질 : 다양한 생리활성의 펩타이드, peptide 또는 polypeptide vaccine, antibody, 세포내 신호전달 관련 단백질, 유전자 발현 관련 단백질, hormone 과 수용체 등 [3] 환경산업관련 효소

8. Protein Engineering (1) Novel and altered functions (2) Physical properties such as enhanced stability (3) Structure based materials Enzymes for pharmaceutical and biotechnology industries Proteins as materials (1) Nanoscale architecture (2) Rich chemistry (3) Versatile enzymatic activities (Protein Molecular Machines) Advances in protein engineering (1) de novo protein design (2) molecular biology (3) non-natural amino acids and peptide ligation (4) protein assembly

9. K. Eric Drexler “Self-replicating Nano Assembler” [PNAS 78, pp 5275-5278 (1981)] - Fabrication of Devices with Protein Molecules - Proteins as a design element Self-assembly Recognition specificity Biofabrication

10. Biological Structures = Nanomaterials

11. Lipids Fatty acids

12. Structural Hierarchy of Protein

13. [Amino acids]

14. [Nonstandard amino acids]

15. [Peptide]

16. Peptide 의 생리활성 Aspartame: aspartate 와 phenylalanine Oxytocin: 자궁수축 Bradykinin: 항염증효과 Enkephalin: 마취성, 통증조절 Insulin, glucagon, somatostatin: Glucose metabolism Tissue specific limited proteolysis of precursor polypeptides (in vivo) Solid phase synthesis (in vitro)

17. [Protein] Noncovalent interactions (1)Ionic interaction (2)Hydrogen bond (3)Hydrophobic interaction (4)van der Waals interaction Stability: minimum energy content high activation energy Structural flexibility – Functional variety Protein folding : Entropy

18. [Denaturation-Renaturation Experiment by Christian Anfinsen]

19. Levinthal’s paradox Folding mechanisms (1)Diffusion-collision (microdomain) model (2)Framework model (3)Hydrophobic collapse model (4)Molten globule model (5)Jigsaw puzzle model

20. [Hydrophobic collapse model]

21. [Molecular Chaperone] Holdase vs. Foldase

22. Structural Hierarchy of Protein

26. [Enzyme] (1)Substrate specificity ( 기질특이성 ) (2)Acceleration of chemical reaction ( 반응가속화 ) (3)Mild conditions ( 온순조건 ) (37 degree and pH 7.4) Rate Enhancement ( 반응속도 증가 ) without affecting Chemical Equilibrium ( 반응평형 ) Binding Energy between Enzyme and Substrate

27. Most biomolecules are quite stable. No reaction w/o enzyme Enzyme: Active site + Other region

28. Enzyme catalyzed reaction: 반응평형 무관, 반응속도만 증가 increase reaction rate without affecting chemical equilibrium cf) mass action ratio G o’ = - RT ln K eq vs. k =  T/h exp (- G ‡ /RT)

30. [Protein-based Suprastructure Formation] Suprastructure

31. Supramolecular Assembly of Proteins

32. Amyloid Fibrils Amyloidogenesis Soluble Proteins Self-assembly

33. Amyloidogenesis Misfolded protein Folded state degradation Accumulation Amyloid formation Degenerative disorders refolding Amino acids Creutzfeldt-Jakob disease [Spongiform encephalopathies]

34. Neurodegenerative disorders The amyloid formation is the common phenomenon observed in various neurodegenerative disorders, including Parkinson’s disease, Alzheimer’s disease, Huntington’s chorea, Amyotrophic lateral sclerosis, Prion disease, etc. Parkinson’s disease Alzheimer’s disease Prion disease [mad cow disease]