Divergent Evolution of (??)8-Barrel Enzymes

Abstract

The (?[alpha)8-barrel is the most versatile and most frequently encountered fold among enzymes. It is an interesting question how the contemporary (?[alpha)8-barrels are evolutionarily related and by which mechanisms they evolved from more simple precursors. Comprehensive comparisons of amino acid sequences and threedimensional structures suggest that a large fraction of the known (?[alpha)8-barrels have divergently evolved from a common ancestor. The mutational interconversion of enzymatic activities of several (?[alpha)8-barrels further supports their common evolutionary origin. Moreover, the high structural similarity between the N and Cterminal (?[alpha)4 units of two (?[alpha)8-barrel enzymes from histidine biosynthesis indicates that the contemporary proteins evolved by tandem duplication and fusion of the gene of an ancestral halfbarrel precursor. In support of this hypothesis, recombinantly produced halfbarrels were shown to be folded, dimeric proteins.

Mimicking enzyme evolution by generating new (βα) 8 -barrels from (βα) 4 -half-barrels

“…It has been postulated that HisA and HisF evolved from a common (␤␣) 4 -halfbarrel by a series of gene duplication and diversification events (4,11). In the present work, the first steps of this hypothetical evolutionary pathway were reconstructed experimentally, by using HisF-C as a model for the ancestral half-barrel (Fig.…”

“…It appears that both HisF and HisA are composed of two structural domains, namely the corresponding N-and C-terminal half-barrels. These results suggest an evolutionary scenario according to which a primordial gene encoding a (␤␣) 4 -half-barrel as a subunit of a homodimeric enzyme was duplicated and fused to yield a monomeric, ancestral (␤␣) 8 -barrel, from which HisF, HisA, and presumably also TrpF evolved by a series of further gene duplication and diversification events (4,11). Moreover, it was postulated that (␤␣) 4 -halfbarrels are independently evolving domains, implying that new (␤␣) 8 -barrels could be generated by mixing and joining (␤␣) 4 half-barrels from an existing pool (18).…”

“…For this reason, and on the basis of comprehensive amino acid sequence comparisons (6,7), it has been postulated that a large fraction of the known (␤␣) 8 -barrels have evolved by gene duplication and diversification (8,9). In particular, similarities in sequence, structure, and function suggest that several (␤␣) 8 -barrels from the tryptophan and histidine biosynthetic pathways have evolved divergently from a common ancestral enzyme (10,11). In support of this hypothesis, both NЈ [(5Ј-phosphoribosyl)formimino]-5-aminoimidazole-4-carboxamide-ribonucleotide (ProFAR) isomerase (HisA) and imidazole glycerol phosphate synthase (HisF), which catalyze two consecutive reactions of histidine biosynthesis, could be converted by exchanging a single amino acid into enzymes with phosphoribosylanthranilate isomerase (TrpF) activity (12,13).…”

Triosephosphate isomerase: a highly evolved biocatalyst

“…The importance of the electrostatic properties of this fold has also been discussed [65,66]. Evolutionary studies [22,25,67] have shown that the TIM-barrel has possibly evolved from two half barrels [68]. Also, recent enzyme design studies [69,70], using either directed evolution [71] or computational approaches [72], highlight the importance of the TIM-barrel fold as an important framework for making non-natural enzymes.…”

Directed evolution of (βα)8-barrel enzymes

“…A scaffold that has caught a lot of attention is the (ba) 8 barrel fold (also known as TIM-barrel). About 10% of all the enzymes with known structure adopt this fold.…”