Τάσος Οικονόµου ιαλεξη 8. Kινηση, λειτουργια, ελεγχος.

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Magdalene Francis
6 years ago
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1 Τάσος Οικονόµου ιαλεξη 8 Kινηση, λειτουργια, ελεγχος

2 εν ξεχνω.

3 Cell

4 The peptide bond

5 Polypeptides are stabilized by: 1. Covalent bonds= amide bond 2. Noncovalent, weakly polar interactions 3. Covalent bonds= disulfide bridges

6 In the absence of water, C=O and N-H bond between them and stabilize regular structures=secondary structure

7 Secondary structure elements = F and Y torsion angles of the backbone repeat in regular patterns

8 Surface water is important for 3D structure

9 Integral membrane proteins in a lipid bilayer membrane (plasma)

10 Folded protein as thermodynamic comrpomise Free energy difference between protein folded and unfolded states is: kj/mol

11 Proteins can be easily unfolded 1. Temperature 2. Mutations (ts) 3. Chaotropes 4. Detergents

12 Noncovalent, weakly polar interactions form and break. This allows polypeptides to be flexible, to breath and water to enter the structure

13 Covalent bonds add stability to polypeptide structures

14 Post-translational modifications can alter structure/stability

15 Domain= autonomous structure

16 Domains can be discontinuous Alanine racemase

17 Multi-Domain proteins derive form gene duplications-fusions-insertions Thioesterase Thioester dehydrase 2 identical domains/1 gene homodimer/1 gene

18 In evolution domains maintain their secondary structure framework but allow changes of their connecting loops

19 Proteins are flexible molecules

20 Conformational fluctuations - Transitions form one folding pattern to another are rare - Ligand bind can stabilize disordered structures - Ligand binding rarely destabilizes ordered structures - Polypeptide subunts may associate/ dissociate upon ligand binding

21 Motions of internal/external protein atoms External >1A Internal <1A flexible rigid

22 Protein motions involve bonded and nonbonded groups

23 Proteins may have distinct alternate states T4 lysozyme

24 Optimal balance of rigidity/flexibility is essential for catalysis GAPDH yeast Thermotoga

25 Ligand-triggered conformational changes Aspartate aminotransferase

26 Lid-like movement over ligand site Text Mobile Lid Triosephosphate isomerase

27 Ligands can drive large-scale conformational changes AMP AMP AMP-PNP Adenyate kinase

28 Protein surface properties and binding sites

29 Proteins work by binding other molecules

30 Binding occurs because of steric and charge complementarity

31 Protein-ligand complementarity Anthrax toxin MAPKK-2 aminoterminal peptide

32 Protein binding site nomenclature: 1. Ligand-binding sites (molecular recongition only) 2. Active sites (molecular recongition and catalysis)

33 Proteins adapt to their ligands Protein kinase A+peptide analogue

34 Protein flexibility/adaptability explains efficiency of some drugs HIV protease haloperidol crixivan Natural peptide

35 Proteins can bind ligands with a wide range of affinities Low K D = 10-3 M High K D = M

36 Binding sites for macromolecules can be multiple

37 Binding sites for macromolecules: protruding helix fits into DNA grooves

38 Binding sites for macromolecules: 1. Large contiguous surface (>100 A2) 2. Multiple surfaces 3. Protruding loops or cavities or flat surfaces

39 Binding sites for small molecules: Clefts, pockets, cavities

40 Catalytic sites often occur at domain and subunit interfaces 3 isopropylmalate dehydrogenase NADPH

41 Binding sites frequently have exposed hydrophobic surfaces Cytochrome c6 Haeme binding pocket

42 Interaction domains control protein flow

43 Ligand binding controls protein function competitive

44 Ligand binding controls protein function cooperative

45 Ligand binding controls protein function cooperative

46 Ligand binding can cause conformational changes at distant sites

47 Allosteric effectors Allosteric inhibitors

48 Transcarbamoylase An allosteric enzyme Carbamoyl phosphate aspartate

49 Protein nucleotide switches control signalling and motions

50 G-proteinSwitching mechanism

51 G-protein Switching mechanism is controlled by other proteins

52 G-proteins

53 DNA polymerase replication factory

54 Cell division: the FtsZ ring

55 Helicases

Protein Structure and Function: From Sequence to Consequence 1. From Sequence to Structure

Protein Structure and Function: From Sequence to Consequence Gregory A. Petsko and Dagmar Ringe, Brandeis University Published by New Science Press Ltd and distributed in the United States and Canada by