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Transcript
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