RESUMO
The atomic structures of two proteins in the histidine biosynthesis pathway consist of beta/alpha barrels with a twofold repeat pattern. It is likely that these proteins evolved by twofold gene duplication and gene fusion from a common half-barrel ancestor. These ancestral domains are not visible as independent domains in the extant proteins but can be inferred from a combination of sequence and structural analysis. The detection of subdomain structures may be useful in efforts to search genome sequences for functionally and structurally related proteins.
Assuntos
Aldose-Cetose Isomerases/química , Aminoidrolases/química , Evolução Molecular , Duplicação Gênica , Estrutura Terciária de Proteína , Recombinação Genética , Aldose-Cetose Isomerases/genética , Aldose-Cetose Isomerases/metabolismo , Motivos de Aminoácidos , Sequência de Aminoácidos , Aminoidrolases/genética , Aminoidrolases/metabolismo , Sítios de Ligação , Catálise , Cristalografia por Raios X , Histidina/biossíntese , Modelos Moleculares , Dados de Sequência Molecular , Dobramento de Proteína , Alinhamento de Sequência , Thermotoga maritima/enzimologiaRESUMO
The (betaalpha)8-barrel is the most versatile and most frequently encountered fold among enzymes. It is an interesting question how the contemporary (betaalpha)8-barrels are evolutionarily related and by which mechanisms they evolved from more simple precursors. Comprehensive comparisons of amino acid sequences and three-dimensional structures suggest that a large fraction of the known (betaalpha)8-barrels have divergently evolved from a common ancestor. The mutational interconversion of enzymatic activities of several (betaalpha)8-barrels further supports their common evolutionary origin. Moreover, the high structural similarity between the N- and C-terminal (betaalpha)4 units of two (betaalpha)8-barrel enzymes from histidine biosynthesis indicates that the contemporary proteins evolved by tandem duplication and fusion of the gene of an ancestral 'half-barrel' precursor. In support of this hypothesis, recombinantly produced 'half-barrels' were shown to be folded, dimeric proteins.