title: A six-stranded double-psi beta barrel is shared by several protein superfamilies.
abstract: BACKGROUND
  Six-stranded beta barrels with a pseudo-twofold axis are found in several proteins. One group comprises a Greek-key structure with all strands antiparallel; an example is the N-terminal domain of ferredoxin reductase. Others involve parallel strands forming two psi structures (the double-psi beta barrel). A recently discovered example of the latter class is aspartate-alpha-decarboxylase (ADC) from Escherichia coli, a pyruvoyl-dependent tetrameric enzyme involved in the synthesis of pantothenate.
  
  
  RESULTS
  Visual inspection and automated database searches identified the six-stranded double-psi beta barrel in ADC, Rhodobacter sphaeroides dimethylsulfoxide (DMSO) reductase, E. coli formate dehydrogenase H (FDHH), the plant defense protein barwin, Humicola insolens endoglucanase V (EGV) and, with a circular permutation, in the aspartic proteinases. Structure-based sequence alignments revealed several interactions including hydrophobic contacts or sidechain-mainchain hydrogen bonds that position the middle beta strand under a psi loop, which may significantly contribute to stabilizing the fold. The identification of key interactions allowed the filtering of weak sequence similarities to some of these proteins, which had been detected by sequence database searches. This led to the prediction of the double-psi beta-barrel domain in several families of proteins in eukaryotes and archaea.
  
  
  CONCLUSIONS
  The structure comparison and clustering study of double-psi beta barrels suggests that there could be a common homodimeric ancestor to ADC, FDHH and DMSO reductase, and also to barwin and EGV. There are other protein families with unknown structure that are likely to adopt the same fold. In the known structures, the protein active sites cluster around the psi loop, indicating that its rigidity, protrusion and free mainchain functional groups may be well suited to providing a framework for catalysis.
authors.affiliation: Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB2 1GA, UK.
authors.forename: R M
authors.initials: RM
authors.lastname: Castillo
authors.forename: K
authors.initials: K
authors.lastname: Mizuguchi
authors.forename: V
authors.initials: V
authors.lastname: Dhanaraj
authors.forename: A
authors.initials: A
authors.lastname: Albert
authors.forename: T L
authors.initials: TL
authors.lastname: Blundell
authors.forename: A G
authors.initials: AG
authors.lastname: Murzin
mesh_terms: D000595:Amino Acid Sequence; D002480:Cellulase / Q000737:chemistry; D005560:Formate Dehydrogenases / Q000737:chemistry; D005968:Glutamate Decarboxylase / Q000737:chemistry; D006864:Hydrogenase / Q000737:chemistry; D007506:Iron-Sulfur Proteins; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes / Q000737:chemistry; D010088:Oxidoreductases / Q000737:chemistry; D010940:Plant Proteins / Q000737:chemistry; D017433:Protein Structure, Secondary; D016415:Sequence Alignment
chemical_list: D007506:Iron-Sulfur Proteins; D009097:Multienzyme Complexes; D010940:Plant Proteins; C076873:barwin protein, Hordeum vulgare; D010088:Oxidoreductases; D006864:Hydrogenase; D005560:Formate Dehydrogenases; C054017:formate hydrogenlyase; C045664:dimethyl sulfoxide reductase; C097231:endoglucanase V; D002480:Cellulase; C019104:aspartate-alpha-decarboxylase; D005968:Glutamate Decarboxylase