1. Protein Structure Lecture 2/26/2003

2. beta sheets are twisted Parallel sheets are less twisted than antiparallel and are always buried. In contrast, antiparallel sheets can withstand greater distortions (twisting and beta- bulges) and greater exposure to solvent.

3. The twist is due to chiral (l)- amino acids in the extended plane. This chirality gives the twist and distorts H- bonding. A tug of war exists between conformational energies of the side chain and maximal H- bonding.

5. Two proteins exhibiting a twisting  sheet Bovine carboxypeptidase Triose phosphate isomerase

6. Connections between adjacent  sheets

7. Sheet facts Repeat distance is 7.0 Å R group on the Amino acids alternate up-down-up above and below the plane of the sheet 2 - 15 amino acids residues long 2 - 15 strands per sheet Ave of 6 strands with a width of 25 Å parallel less stable than anti-parallel Anti-parallel needs a hairpin turn Tandem parallel needs crossover connection which has a right handed sense

8. Non-repetitive regions Turns - coils or loops link regions of secondary structure 50% of structure of globular proteins are not repeating structures  bends type I and type II :hairpin turn between anti parallel sheets

9. Reverse Turns Type I  2 = -60 o,  2 = -30 o  3 = -90 o,  3 = 0 o Type II  2 = -60 o,  2 = 120 o  3 = 90 o,  3 = 0 o

10. two-residue turns

11. Protein Structure Terminology

12. Folding motifs (super secondary structure) Certain amino sequences have patterns to their folding. A.  motif, B.  hairpin C.  motif

13. beta-alpha-beta parallel beta-strands connected by longer regions containing alpha-helical segments almost always has a right-handed fold

14. Helix-turn-helix loop regions connecting alpha-helical segments can have important functions e.g. EF-hand and DNA-binding EF hand loop ~ 12 residues polar and hydrophobic a.a. conserved positions Glycine is invariant at the sixth position The calcium ion is octahedrally coordinated by carboxyl side chains, main chain groups and bound solvent

15. Protein Folds There is an estimate of about 10000 different folding patterns in proteins About half of the proteins fall into a few dozen folding patterns. Those proteins related by structure are called families. A large Family are the c cytochromes (see Figure 6-31 pg 147 in FOB.)

16. The  barrel has several types of structures that have been mimicked in art. A. rubredoxin B. Human prealbumin or porins C. Triose phosphate isomerase

17. Concanavalin A Mostly a  barrel motif

18. Carbonic anhydrase H 2 CO 3 -  CO 2 + H 2 O

19. Nucleotide binding-Rossmann Fold

20. Glyceraldehyde-3- phosphate dehydrogenase Binding NADH in the Rossmann fold.

21. Zinc fingers C 2 H 2 zinc finger: It is characterized by the sequence CX 2-4 C....HX 2-4 H, where C = cysteine, H = histidine, X = any amino acid. C 4 zinc finger: Its consensus sequence is CX 2 CX 13 CX 2 CX 14- 15 CX 5 CX 9 CX 2 C. The first four cysteine residues bind to a zinc ion and the last four cysteine residues bind to another zinc ion C 6 zinc finger. It has the consensus sequence CX 2 CX 6 CX 5- 6 CX 2 CX 6 C. The yeast's Gal4 contains such a motif where six cysteine residues interact with two zinc ions

22. C2H2 zinc finger

23. Zinc Finger DNA-binding

24. Summary Chapter 6 Four levels of protein structure –Primary –Secondary –Tertiary –Quaternary Peptide bond (  bond) Sheets and helices (  and  bonds) Tertiary structure (fibrous or globular) Structure determination and fold space Protein folding discussed after kinetics -lecture 19