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Protein Folding of A Biopharmaceutical — hCD83

Protein Folding of A Biopharmaceutical — hCD83. Lin Zhang Chemical Engineering Department. Biopharmaceuticals. Proteins In use: Insulin tPA Potential use: Human CD83. Outlines. Backgrounds of hCD83 Preliminary Results and Discussion.

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Protein Folding of A Biopharmaceutical — hCD83

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  1. Protein Folding of A Biopharmaceutical — hCD83 Lin Zhang Chemical Engineering Department

  2. Biopharmaceuticals Proteins In use: Insulin tPA Potential use: Human CD83

  3. Outlines • Backgrounds of hCD83 • Preliminary Results and Discussion

  4. Human CD83 (hCD83) • Human CD83 is expressed predominantly on the surface of dendritic cells (DCs) • DCs are the most potent antigen presenting cells of the immune system • Glycoprotein CD83 is one of the best-known maturation markers for human DCs

  5. Backgrounds hCD83 Argos DC Bio Preclinical Trial Production

  6. Backgrounds Insulin

  7. Backgrounds What we are interested in: • Dynamic process of protein folding • Protein Aggregation • 3D Structure

  8. Backgrounds FDA Approval 3D Structure Crystallography

  9. 3D Structure Prediction Flowchart Target Sequence Conserved Domain Yes No Homologous in PDB Secondary Structure Ⅰ Ⅱ Comparison Comparative Modeling Tertiary Structure

  10. Preliminary Results Descriptions Database Searching Protein-Protein Blast

  11. Preliminary Results

  12. Preliminary Results 1MCP_H • Class: All beta proteins • Fold: Immunoglobulin-like beta-sandwich sandwich; 7 strands in 2 sheets; greek-keysome members of the fold have additional strands • Superfamily: Immunoglobulin (IG) • Family: V set domains (antibody variable domain-like) 1GL4_B • Class: All beta proteins • Fold: Immunoglobulin-like beta-sandwich sandwich; 7 strands in 2 sheets; greek-keysome members of the fold have additional strands • Superfamily: Immunoglobulin (IG) • Family: I set domains

  13. Preliminary Results Protein fold recognition Phyre 1nez_g

  14. Preliminary Results Ⅰ Comparative Modeling Swiss-Model RAPTOR

  15. Preliminary Results Swiss-Model 1MCP_H (7~121)

  16. Preliminary Results Swiss-Model 1a6w_L

  17. Discussion Common

  18. Discussion Differences 1MCP_H 1α-helix e f

  19. Discussion Differences 1a6w_L b c 2α-helices e f

  20. Preliminary Results RAPTOR 1a49_a

  21. Preliminary Results 1a49_a 1 α-helix: e f : Thr(83)~Ser(87)

  22. Preliminary Results Ⅱ Secondary Structure and Tertiary Structure Secondary Structure: PHD and Jnet Tertiary Structure : HMMSTR

  23. Preliminary Results PHD

  24. Preliminary Results Jnet

  25. Discussion Secondary Structure PHD: 6 β-strands, no α-helix, not to be globular protein V(8)~V(10), D(17)~C(20), V(32)~K(36), S(76)~N(81), T(89)~L(94), V(107)~T(112) Jnet: 8 β-strands, no α-helix V(8)~C(12), D(15)~T(21), T(31)~K(36), E(43)~T(47) N(64)~D(68), Y(75)~N(81), T(89)~Q(95), G(104)~T(112)

  26. Preliminary Results HMMSTR

  27. Discussion HMMSTR 3 α- helices: Asp(98)~Asn(102) Pro(115)~Arg (118) Lys(119)~Ile(130)

  28. Discussion Comparison A.Fold Pattern Comparative Modeling: distinguished hydrophobic core and hydrophilic side, regular, tight HMMSTR: irregular, loose pattern, no related motif

  29. Discussion Comparison B.Composition Comparative Modeling:more beta-strands and loops as well as hydrogen bonds HMMSTR: less beta-strands, loops and hydrogen bonds

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