1. Principles of Protein Structure

2. AMINOACIDS

3. Estereoisomer L Side-chain (-CH 3 ) }carboxyl-COOH amino amino -NH 2

6. PEPTIDE BOND

7. Peptide bond | O | || _ --C — N-- | H _ | O | | --C == N-- | H-+ P LANE -CO-NH-

8. Angles  i   = [-180º, +180º ]  = [-180º, +180º ]

9. Native Conformation

10. STRUCTURE

12. Hydrogen Bond INTRA-CHAININTER-CHAIN CloseFar { donor acceptor

13. SECONDARYSTRUCTURE

14. Chain  CtNt Sheet 

15. Helix Helix  H ELIX Helix 3 10 1 2 3 1 2 3 4 4 5 Turn-3 3 Aa 3.6 Aa Turn-4 HELIX

16. N-cap box HbondHidrophobic N c -N 3 N’-N 4 Big box N c -N 3 N’’-N 4 Shellman C’’-C 3 C’-C 2 C’’-C 3 LL C’-C 3 C’’-C 3

18. RAMACHANDRAN MAP    

19. PROPENSITY

20. Xray diffraction X ray = 3DStructure FourierSynthesis Crystal

21. PROTEIN CLASSIFICATION

22. MIOGLOBIN MIOGLOBIN Hydrofobic Core Core

23. ENERGY

24. HYDROFOBIC EFFECT: zone hydroph. C LATRATE Waterfree S S S S

25. FOLDS

26. TriosePhosphateIsomerase Carboxypeptidase Glucanase Ribonuclease Mioglobin

27. SUPERSECUNDARY STRUCTURE

28. MOTIF: Cluster of 2-4 regular secondary structures usually involved in a particular function Exemple: EF hand  hairpin Ca +2 binding loop

31. Exemple: hairpin  hairpin  Turn  2 Aa Gly TIPE I’ H.B. lost TIPE II

34. Binding of

36. DOMAIN

37. Baldomero Oliva Miguel

42. Sequence FunctionStructure Function - Structure - Sequence Orthology

43. Sequence Function Structure Convergence (Analogy) Function - Structure - Sequence

44. Sequence Function Structure convergence? Function - Structure - Sequence

45. Sequence Function Structure Remote Homology superfamily Function - Structure - Sequence

46. Sequence Function Structure Diversity Function - Structure - Sequence

47. Sequence Function Structure Paralogs Function - Structure - Sequence

48. Sequence Function Structure Annotation problem Function - Structure - Sequence

49. UCL, Janet Thornton & Christine Orengo Class (C), Architecture(A), Topology(T), Homologous superfamily (H) Protein Structure Classification CATH - Protein Structure Classification [ http://www.biochem.ucl.ac.uk/bsm/cath_new/ ] SCOP - Structural Classification of Proteins MRC Cambridge (UK), Alexey Murzin, Brenner S. E., Hubbard T., Chothia C. created by manual inspection comprehensive description of the structural and evolutionary relationships [ http://scop.mrc-lmb.cam.ac.uk/scop/ ]

50. Baldomero Oliva Miguel SCOP Family Superfamily Fold Class CATH Architecture Topology Superfamily Class

51. TSS toxin 8.8% Id RemoteHomology Cholera toxin 80% Id Homology Baldomero Oliva Miguel SCOP Family Superfamily Fold Class Enterotoxin Aminoacyl tRNA synthetase 4.4% Id Analogs

52. Class(C) derived from secondary structure content is assigned automatically Architecture(A) describes the gross orientation of secondary structures, independent of connectivity. Topology(T) clusters structures according to their topological connections and numbers of secondary structures Homologous superfamily (H)

53. ROSSMANFOLD

54. It binds mononucleotides (NAD, FAD, FMN, etc.). Rossman fold of flavodoxin

55. TRIOSEPHOSPHATEISOMERASE

56. HIGHLY STABLE FOLD TIM BARREL

57. All 

62. 4 helix bundle

63. Globin-like fold Hydrophobic core Active site

64. All 

65. Topological diagram

66.  -propeller

69. Greek key  sandwich  -cristallin

70. Greek key Jelly-roll

73.  -sandwich : Immunoglobulin-like

74. Variable Domain Constant Domain

75. Antibody CDR

76. 

79. Open Sheet

80. Active site found in the Topological Switch

82. 

85. Membrane Proteins

87. integral periferic

88. Integrals: - helix-transmembrane. -  sheet transmembrane.

89. Helix transmembrane Helix transmembrane

90. Porin  sheet transmembrane  sheet transmembrane

91. Peripheral: