Protein Structure Lecture 2/26/2003. beta sheets are twisted Parallel sheets are less twisted than...
Transcript of Protein Structure Lecture 2/26/2003. beta sheets are twisted Parallel sheets are less twisted than...
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Protein Structure
Lecture 2/26/2003
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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.
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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.
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Two proteins exhibiting a twisting sheet
Bovine carboxypeptidase
Triose phosphate isomerase
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Connections between adjacent sheets
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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
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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
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Reverse Turns
Type I 2 = -60o, 2 = -30o
3 = -90o, 3 = 0o
Type II 2 = -60o, 2 = 120o
3 = 90o, 3 = 0o
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two-residue turns
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Protein Structure Terminology
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Folding motifs (super secondary structure)
Certain amino sequences have patterns to their folding.
A. motif, B. hairpin C. motif
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beta-alpha-beta
• parallel beta-strands connected by longer regions containing alpha-helical segments
• almost always has a right-handed fold
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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
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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.)
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The barrel has several types of structures that have been mimicked in art.
A. rubredoxin
B. Human prealbumin or porins
C. Triose phosphate isomerase
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Concanavalin A
Mostly a barrel motif
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Carbonic anhydrase
H2CO3 - CO2 + H2O
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Nucleotide binding-Rossmann Fold
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Glyceraldehyde-3-phosphate dehydrogenase
Binding NADH in the Rossmann fold.
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Zinc fingers
C2H2 zinc finger: It is characterized by the sequence CX2-4C....HX2-4H, where C = cysteine, H = histidine, X = any amino acid.
C4 zinc finger: Its consensus sequence is CX2CX13CX2CX14-
15CX5CX9CX2C. The first four cysteine residues bind to a zinc ion and the last four cysteine residues bind to another zinc ion
C6 zinc finger. It has the consensus sequence CX2CX6CX5-6CX2CX6C. The yeast's Gal4 contains such a motif where six cysteine residues
interact with two zinc ions
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C2H2 zinc finger
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Zinc Finger DNA-binding
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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