Smart Enzyme Design and Protein Self-assembly: Dynamic Biomimetic Materials

Transcription

1 超分子结构与材料国家重点实验室 State Key Laboratory of Supramolecular Structure and Materials, Jilin University Annual Seminar of Programmable Materials (OMA) Smart Enzyme Design and Protein Self-assembly: Dynamic Biomimetic Materials Junqiu Liu State Key Laboratory of Supramolecular Structure and Materials, Chemistry College, Jilin University, China Nov Finland

2 Outline Enzyme Design Protein Assembly Recognation Interaction High activity; High stability

3 Research motivation Recognition Model mimic Static state Enzyme Design High activity; High stability; High coordination Accurate mimicking Allosteric state Enzyme Application Enzyme regulation: self-assembly;hydrogel; nanostuctures Janne A. Ihalainen etal, Nature 2014

4 Self-assembly I Biomimetic self-assembly II I. Biomimetic enzymes; II. Biomimetic light-harvesting system; III.Biomimetic muscle III

5 Recogniation Catalytic group

6 Biomimetic Enzyme Design Isomerase Phosphate Synthase Fersht A R. * etal. Nature 2000, 403,617

7 Dynamic Biomimetic Enzyme Design Leigh D A. * etal, Science 2013, 339, 189

8 I Enzyme Design Glutathione Peroxidase (GPx) GPx catalyzed reaction: ROOH + 2GSH ROH + H2O + GSSG Active site GSH Recognition site GPx Active Site

9 Enzyme and Artificial Enzyme Design Molecular System Liu* etal. J. Am. Chem. Soc. 2004, 126, Liu* etal. J. Am. Chem. Soc. 2004, 126, Liu* etal. J. Am. Chem. Soc. 2005, 127, Liu Wulff*. J. Am. Chem. Soc. 2004, 126, 7452 Liu Wulff *. Angew.Chem.Int. Ed. 2004, 43, 1287 Liu* Wulff*. J. Am. Chem. Soc. 2008, 130, 8044 Supramolecular System Liu* etal. Angew. Chem. Int. Ed. 2009, 48, 2020 Liu* etal. Angew.Chem.Int. Ed. 2010, 49, 3920 Liu* etal. ACSnano, 2012, 2013, 2014, 2015 Liu* etal. Angew.Chem.Int. Ed. 2013, 52,5590 Liu* etal. J. Am. Chem. Soc. 2013, 135, Liu* etal. Angew. Chem. Int. Ed. 2014, 13536

10 1. Design on natural protein Catalytic site 识别部位 Binding site GPx activity of Telluro-GST Introduce catalytic site into binding site GS Te-GST T Ser9 Cys9 TeCys9 c a t a l y s t h y d r o p e r o x i d e a c t i v i t y P Z 51 H 2 O 2 1 G S T 0 S e - G S T 3000 Te-GST 6000 N a t i v e G P X 5780 Liu* et al. Angew. Chem. Int. Ed. 2009,48,2020; Chem. Soc. Rev. 2011, 40, 1171

11 2. Smart enzyme design Calcium ion switched selenoenzyme design Luo*, Liu* et al. Angew. Chem. Int. Ed. 2014,

12 ATP-switched smart selenoenzyme design Anti-mitochondrial damage model Adenylate kinase A) B)

13 3. Enzyme Design on Protein Assemblies Enzyme design on natural protein nanotube Design an active site Self-assembly Hou, Liu* etal, ACSnano, 2012, 6, 8692

14 4. Enzyme design by self-assembly

15 Enzyme design on giant nanotubes with molecular imprinting GPx activity Catalysts Substrate Relative activity PhSeSePh TNB 1 NT(1,2) TNB 0 NT (1,2bSe) TNB NT (1,2bTe) TNB NT (1,2bTe,2c) TNB Liu* etal, Angew.Chem.Int. Ed. 2010,49,3920

16 Construct of the thermosensitive nanoenzyme Self-Assembly Thermosensitive nanostructures construct between the Nanotubes and Vesicle-like Structures Self-Assembly

17 Turn on/ off enzyme activity

18 5. Enzyme design on self-assembled peptides Amphiphilic peptide self-assembly

19 Liu*, Zou*, etal, ACSnano, 2014, 11715

20 6. Mimicking Helice Structure Dong *, Liu * et al. Angew. Chem. Int. Ed. 2015, 3140

21 Liu* etal. Chem. Soc. Rev. 2011, 40, 1171 (Invited review; Inside Front Cover) Top ten accessed articles Liu* etal. Chem. Soc. Rev. 2012, 41, 7890 (Invited review) Liu, Shen, etal. Chem Soc Review, 2010, In press

22 7. Stablization of Transition-state by Molecularly Imprinting Kcat / K uncat N 1 N H 100 TS Recognition Site 4040 N N H 2 N N H 2 N H 2 Catalytic sites in TS site N N H H 2 N N 3 N H N 功能单体 Liu* Wulff * J. Am. Chem. Soc. 2008, 130, 8044 (Top 10 Articles Published in the Same Domain, No.1)

23 Artificial active site Energy levels in catalysis Wulff*, Liu* Acc. Chem. Res. 2012,45,239 (Invited review,front cover )

24 II Protein Assembly How to control the protein-protein interaction Protein protein Interaction face How to control the orientation of the protein assembly

25 Protein Self-Assembly with Atomic Level Accuracy D Baker etal. Science 2012, 336, 1175

26 Enzyme Design on Protein assembly in vivo With in vivo activity Tezcan F. A. etal, Science 2014, 346, 1525

27 1. Protein Assembly by Host- guest Interaction

28 Enzyme functionality Liu* etal Angew.Chem.Int. Ed. 2013, 52,5590

29 Control the orientation of the protein assemblies Host-guest interaction Unpublished results

30 2. Accurate Control of Protein Self-assembly

31 a 1 b Metal ion site 2 3 noncovalent interaction network 4 5 c nanoring Self-assembly Metal coordination site

32 All rings Diameter of 367nm GST Dimer 4.2 nm Liu* etal. J. Am. Chem. Soc. 2013, 135, (Highlight by Nature China)

33 Control of the size of nanorings

34 4. Control the dynamic motion Protein nanospring Ca 2+ - binding protein Unpublished results

35 5. Charge Drived Protein Assembly Mimicking light-harvesting system by Quantum Dots _ 11nm 3nm _ nm Liu* etal. ACS Nano, 2014, 8, 3743

36 Self-Assembly Induced by Soft Nanoparticles Enzyme coorperation on protein assembly GPx SOD Liu* etal. ACS Nano, 2015, 9, 5461

37 Self-Assembly of Cricoid Proteins Induced by Soft Nanoparticles Mimicking light-harvesting system Liu* etal. ACS Nano, 2015, revised

38 III Design of 2D Protein Assemblies 1. Zn 2+ binding models through metal coordination Zn 2+ /protein 20:1 20:1 40:1 40:1 Smac protein 50:1 50:1 AFM images of assemblies

39 3. Enzyme Regulation Protein Hydrogel Self-Healing Enzymes cooperation Glucose oxidase (GOX) Catalase (CAT)

40 Self-healing behavior of protein hydrogel Liu* etal Angew.Chem.Int. Ed. 2014, 53, (Hot paper)

41 Summary Enzymes Design Host-Guest artificial enzymes; Suparmolecular artificial enzymes; Mechanism study of the nature of enzyme catalysis; Cooperation between recognition and catalysis Protein Assembly Enzyme design and artificial enzymes; Protein assembly structure; Light-harvesting system;

42 Acknowledgment Collaborators: Prof. Jiacong Shen; Prof. Guimin Guo Prof. August Bock, Lehrstuhl fur Mikrobiologie der Universitat Munchen Prof. Louis A. Pete Silks, Los Alamos National Laboratory Prof. Gunter Wulff, Institute of Organic and Macromolecular Chemistry, Germany. Prof. Xi Zhang. Tsinghua University, China Dr. Zheyuan Dong, Huijun Yu, Shizhong Mao Ph.D.Student, Jing Li, Xin Huang, Xiaoman Liu, Yan Ge, Xiangqiu Li, Ping Wu, Zhiming Zhang,Xiaoguang Wang, Yuetong Ji Ms.Studant, Chunqiu Zhang,Yongguo Wang, Yong Tang, Zhenhui Qi, Financial support: The National Natural Science Foundation The High Technology Research Development Plan The Major State Basic Research Development Program

43 Liu s Research Group ( 刘俊秋教授研究组 )

44 吉林大学超分子结构与材料教育部重点实验室 Key Laboratory for Supramolecular Structure and Materials Thank you!