A common evolutionary origin of two elementary enzyme folds.
The (beta alpha)(8)-barrel is the most frequent and most versatile fold among enzymes [Höcker et al., Curr. Opin. Biotechnol. 12 (2001) 376-381; Wierenga, FEBS Lett. 492 (2001) 193-198]. Structural and functional evidence suggests that (beta alpha)(8)-barrels evolved from an ancestral half-barrel, which consisted of four (beta alpha) units stabilized by dimerization [Lang et al., Science 289 (2000) 1546-550; Höcker et al., Nat. Struct. Biol. 8 (2001) 32-36; Gerlt and Babbitt, Nat. Struct. Biol. 8 (2001) 5-7]. Here, by performing a comprehensive database search, we detect a striking and unexpected structural and amino acid sequence similarity between (beta alpha)(4) half-barrels and members of the (beta alpha)(5) flavodoxin-like fold. These findings provoke the hypothesis that a large fraction of the modern-day enzymes evolved from a basic structural building block, which can be identified by a combination of sequence and structural analyses.
Höcker
Birte
B
Universität zu Köln, Institut für Biochimie, Cologne, Germany.
Schmidt
Steffen
S
Sterner
Reinhard
R
D019295:Computational Biology; D030562:Databases, Protein; D004798:Enzymes / Q000502:physiology*; D004926:Escherichia coli; D019143:Evolution, Molecular; D005418:Flavodoxin / Q000737:chemistry; D008958:Models, Molecular; D011424:Propionibacterium; D017510:Protein Folding; D017386:Sequence Homology, Amino Acid; D013329:Structure-Activity Relationship; D020124:Thermotoga maritima
D004798:Enzymes; D005418:Flavodoxin