Principles of Protein Structure AMINOACIDS Estereoisomer L Side-chain (-CH 3 ) }carboxyl-COOH amino amino -NH 2 PEPTIDE BOND Peptide bond | O | || _ --C N-- | H _ | O | | --C == N-- | H-+ P LANE -CO-NH- Angles i = [-180, +180 ] = [-180, +180 ] Native Conformation STRUCTURE Hydrogen Bond INTRA-CHAININTER-CHAIN CloseFar { donor acceptor SECONDARYSTRUCTURE Chain CtNt Sheet Helix Helix H ELIX Helix Turn-3 3 Aa 3.6 Aa Turn-4 HELIX 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 LL C-C 3 C-C 3 RAMACHANDRAN MAP PROPENSITY Xray diffraction X ray = 3DStructure FourierSynthesis Crystal PROTEIN CLASSIFICATION MIOGLOBIN MIOGLOBIN Hydrofobic Core Core ENERGY HYDROFOBIC EFFECT: zone hydroph. C LATRATE Waterfree S S S S FOLDS TriosePhosphateIsomerase Carboxypeptidase Glucanase Ribonuclease Mioglobin SUPERSECUNDARY STRUCTURE MOTIF: Cluster of 2-4 regular secondary structures usually involved in a particular function Exemple: EF hand hairpin Ca +2 binding loop Exemple: hairpin hairpin Turn 2 Aa Gly TIPE I H.B. lost TIPE II Binding of DOMAIN Baldomero Oliva Miguel Sequence FunctionStructure Function - Structure - Sequence Orthology Sequence Function Structure Convergence (Analogy) Function - Structure - Sequence Sequence Function Structure convergence? Function - Structure - Sequence Sequence Function Structure Remote Homology superfamily Function - Structure - Sequence Sequence Function Structure Diversity Function - Structure - Sequence Sequence Function Structure Paralogs Function - Structure - Sequence Sequence Function Structure Annotation problem Function - Structure - Sequence UCL, Janet Thornton & Christine Orengo Class (C), Architecture(A), Topology(T), Homologous superfamily (H) Protein Structure Classification CATH - Protein Structure Classification [] 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 [] Baldomero Oliva Miguel SCOP Family Superfamily Fold Class CATH Architecture Topology Superfamily Class 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 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) ROSSMANFOLD It binds mononucleotides (NAD, FAD, FMN, etc.). Rossman fold of flavodoxin TRIOSEPHOSPHATEISOMERASE HIGHLY STABLE FOLD TIM BARREL All 4 helix bundle Globin-like fold Hydrophobic core Active site All Topological diagram -propeller Greek key sandwich -cristallin Greek key Jelly-roll -sandwich : Immunoglobulin-like Variable Domain Constant Domain Antibody CDR Open Sheet Active site found in the Topological Switch Membrane Proteins integral periferic Integrals: - helix-transmembrane. - sheet transmembrane. Helix transmembrane Helix transmembrane Porin sheet transmembrane sheet transmembrane Peripheral: