PHA111 Protein Structure.pptx

MPharm Programme Protein Structure Dr. Mark Gray Slide 1 of 30 MPharm PHA111 Protein Structure Protein Primary Structure: Amino Acid Sequence • A Pentapeptide: Ser-Gly-Tyr-Ala-Leu Slide 2 of 30 MPharm PHA111 Protein Structure Insulin Slide 3 of 30 MPharm PHA111 Protein Structure Disulphide...

MPharm Programme Protein Structure Dr. Mark Gray Slide 1 of 30 MPharm PHA111 Protein Structure Protein Primary Structure: Amino Acid Sequence • A Pentapeptide: Ser-Gly-Tyr-Ala-Leu Slide 2 of 30 MPharm PHA111 Protein Structure Insulin Slide 3 of 30 MPharm PHA111 Protein Structure Disulphide bonds in hair Slide 4 of 30 MPharm PHA111 Protein Structure How can we describe something this complex? Slide 5 of 30 MPharm PHA111 Protein Structure Protein Secondary Structure: Hydrogen Bonding • X-ray structures of fibrous proteins and small peptides revealed the two main types of secondary structure. • These are the a-helix and the b-sheet. • They are formed by hydrogen bonds between peptides. Slide 6 of 30 MPharm PHA111Protein Structure Keratin Slide 7 of 30 MPharm PHA111 Protein Structure a-keratin (hair) has an a-helix Slide 8 of 30 MPharm PHA111 Protein Structure All protein a-helices are RIGHT HANDED Slide 9 of 30 MPharm PHA111 Protein Structure b-keratin (silk) contains b-sheets Slide 10 of 30 MPharm PHA111 Protein Structure b-sheets come in two main varieties Slide 11 of 30 MPharm PHA111 Protein Structure Other common secondary structures Slide 12 of 30 MPharm PHA111 Protein Structure Linking things together Slide 13 of 30 MPharm PHA111 Protein Structure But what about more complex proteins? • Max Perutz and Sir John Kendrew, Nobel Prize in Chemistry, 1962. • Sperm Whale Myoglobin: first globular protein diffraction pattern (1958). Slide 14 of 30 MPharm PHA111 Protein Structure It’s hard to grow protein crystals • The best crystals of RNaseA were grown in space! • Microgravity and the absence of convection currents give larger and better quality crystals. • NMR has become a useful alternative to X-ray techniques. Slide 15 of 30 MPharm PHA111 Protein Structure Classifying peptide conformations Slide 16 of 30 MPharm PHA111 Protein Structure Proline can cause problems Slide 17 of 30 MPharm PHA111 Protein Structure A Ramachandran Plot for L-Ala Slide 18 of 30 MPharm PHA111 Protein Structure Common secondary structures take up distinctive positions. Slide 19 of 30 MPharm PHA111 Protein Structure Ramachandran diagram for rabbit pyuvate kinase. • Glycine positions are not shown. • This is common practice in these diagrams. • Gly has much more conformational freedom than the other aa. Slide 20 of 30 MPharm PHA111 Protein Structure Protein Tertiary Structure: Packing of Secondary Structures • Myoglobin was found to contain several different a-helices. • These are packed together to give a dense globular morphology. • The interactions commonly used: van der Waals, hydrophobic, electrostatic, hydrogen bonds. Slide 21 of 30 MPharm PHA111 Protein Structure Common tertiary structures Slide 22 of 30 MPharm PHA111 Protein Structure Slide 23 of 30 MPharm PHA111 Protein Structure a/b – Parallel b-sheets Slide 24 of 30 MPharm PHA111 Protein Structure a+b – antiparallel b-sheets Slide 25 of 30 MPharm PHA111 Protein Structure Quaternary Structure: Multiple strands of Amino Acids • Hemoglobin is made up of 4 separate myoglobin like strands. • Each strand has a heme unit used to transport oxygen. • These strands are held together by non-covalent forces. Slide 26 of 30 MPharm PHA111 Protein Structure Common interactions within proteins Slide 27 of 30 MPharm PHA111 Protein Structure Many proteins can spontaneously regain shape after denaturation. Slide 28 of 30 MPharm PHA111 Protein Structure Proteinaceous infectious only protein (PrP or Prion) • Causes spongiform encepalopathies • Most famous diseases are BSE, Scrapie and CJD. • No encoding is needed from nucleic acids c.f. viruses, bacteria, fungi. Slide 29 of 30 MPharm PHA111 Protein Structure Summary Slide 30 of 30 MPharm PHA111 Protein Structure