Alpha/Beta structures

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Alpha/Beta structures

• Barrels, sheets and horseshoes

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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

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TIM barrel
First observed in enzyme Triosephosphate Isomerase
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The core of TIM barrel

• Core is tightly packed with hydrophobic amino
  acids
• Three layers of sidechains

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Residue distribution in TIM barrel
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Unusual exception

• Methylmalonyl-Coenzyme A mutase has small
  hydrophilic residues in the inside of barrel
• Coenzyme A (green) binds in the barrel

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TIM barrel as a domain

• TIM barrel is always associated with enzymatic
  function

Pyruvate kinase
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Location of active site in TIM barrels
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Double barrels

• Phosphoribosyl anthranilate (PRA) isomerase and
  Indoglycerol phosphate (IGP) synthase in E.coli
  (enzyme catalysing two reactions in the
  tryptophan biosynthesis)

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Some other microorganisms have two separate
single-barrel proteins
Barrel 1
Some microorganisms have triple barrel homologous
protein, where the third barrel catalyzes still
another reaction in Trp synthesis pathway
Barrel 2
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TIM barrels example of enzyme evolution

• There is evidence that new enzymes can evolve by
  changing the active site of TIM barrel

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Both enzymes are TIM barrels with 26 sequence
identity
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a/b-horseshoe fold

• a/b horseshoe

Present in many proteins with completely
unrelated functions
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Number of b-a-b repeats can vary considerably
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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

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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

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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
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Topology

• In TIM barrels and horseshoe proteins the
  topology is fixed
• In open sheets topology can vary a lot

TIM
Open a/b sheet
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Location of active site in a/b open twisted sheet
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Sandwiches.... mmmm
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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

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Whats that?

• TATA box binding protein (TBP) is a ... sandwich
• Thats right, a-b double

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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