Transcript Alpha/Beta structures

Alpha/Beta structures
Barrels, sheets and horseshoes
Common features
• Parallel b strands are arranged in barrels or
sheets
• Individual b strands are connected by a
helices
• b-a-b 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
• MethylmalonylCoenzyme 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
a/b-horseshoe fold
a/b horseshoe
ordinary horseshoe
Present in many proteins with completely unrelated functions
Number of b-a-b repeats can vary
considerably
Hydrophobic core of a/b horseshoe
• In between b strands and
helices, NOT in the middle
of horseshoe
• Many leucines in
conserved positions
• a/b 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
a/b open twisted sheet
• Parallel or mixed b-sheet with a helices on both
sides
• Number of b-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 a/b sheet
Location of active site in a/b
open twisted sheet
Sandwiches.... mmmm
Protein structure sandwiches
• Layered molecules, where each layer represents
either a or b structure
• Represents one of “A” levels in CATH
classification
• Most common:
• a-b double sandwich
• a-b-a triple sandwich
• b double sandwich
• Open a/b sheets can be considered.....
• a-b-a sandwiches
What’s that?
• TATA box binding protein (TBP) is a ... sandwich
• That’s right, a-b double
End of story? No other a/b
proteins?
• There is a good deal of other a/b proteins
• However, most of them have folds with
very few representatives, so they will be not
discussed here