Alpha/Beta structures Barrels, sheets and horseshoes.
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Transcript of Alpha/Beta structures Barrels, sheets and horseshoes.
Alpha/Beta structures
Barrels, sheets and horseshoes
Common features
• Parallel strands are arranged in barrels or sheets
• Individual strands are connected by helices
• motif is a building unit
TIM barrel
First observed in enzyme Triosephosphate Isomerase
The core of TIM barrel
• Core is tightly packed with hydrophobic amino acids
• Three layers of sidechains
Residue distribution in TIM barrel
Unusual exception
• Methylmalonyl-Coenzyme A mutase has small hydrophilic residues in the inside of barrel
• Coenzyme A (green) binds in the barrel
TIM barrel as a domain
• TIM barrel is always associated with enzymatic function
Pyruvate kinase
Location of active site in TIM barrels
Double barrels
• Phosphoribosyl anthranilate (PRA) isomerase and Indoglycerol phosphate (IGP) synthase in E.coli (enzyme catalysing two reactions in the tryptophan biosynthesis)
Barrel 1
Barrel 2
Some other microorganisms have two separate single-barrel proteins
Some microorganisms have triple barrel homologous protein, where the third barrel catalyzes still another reaction in Trp synthesis pathway
TIM barrels: example of enzyme evolution
• There is evidence that new enzymes can evolve by changing the active site of TIM barrel
Both enzymes are TIM barrels with 26% sequence identity
ordinary horseshoe
-horseshoe fold
horseshoe
Present in many proteins with completely unrelated functions
Number of repeats can vary considerably
Hydrophobic core of horseshoe
• In between strands and helices, NOT in the middle of horseshoe
• Many leucines in conserved positions
• horseshoe proteins are called also LRR (leuine rich repeats) proteins
Leucine-rich motif in the horseshoe
• a- aliphatic amino acid• X- any amino acid• The motif is strong enough to be used in structure
prediction
open twisted sheet
• Parallel or mixed -sheet with helices on both sides
• Number of -strands vary from 4 to 10• Called also Rossman fold
Lactate dehydrogenase
Topology
• In TIM barrels and horseshoe proteins the topology is fixed
• In open sheets topology can vary a lot
TIM
Open sheet
Location of active site in open twisted sheet
Sandwiches.... mmmm
Protein structure sandwiches
• Layered molecules, where each layer represents either or structure
• Represents one of “A” levels in CATH classification• Most common: • double sandwich• triple sandwich• double sandwich• Open sheets can be considered..... • sandwiches
What’s that?
• TATA box binding protein (TBP) is a ... sandwich
• That’s right, double
End of story? No other proteins?
• There is a good deal of other proteins
• However, most of them have folds with very few representatives, so they will be not discussed here