Divergent Evolution of (␤␣) 8 -barrel Enzymes

lationship), superfamilies (probable common evolutionary origin) and folds (Murzin et al., 1995). Proteins are defined to have a common fold if they have the same major secondary structures in the same spatial arrangement and the same topological connections. SCOP currently distinguishes between several hundred different folds. The (βα)8(or TIM-)barrel is a frequently encountered fold, which comprises about 10% of all known protein structures (Gerlt, 2000). (βα)8-barrel enzymes catalyse a vast range of different reactions, functioning as either oxidoreductases, transferases, hydrolases, lyases or isomerases (Pujadas and Palau, 1999; Wierenga, 2001). The (βα)8-barrel consists of a core of eight twisted parallel βstrands, the β-barrel, which are connected by eight α-helices which form the outer layer of the structure (Figure 1). In all known (βα)8-barrel enzymes, the active site residues are located at the C-terminal face of the β-barrel and within the loops that connect the β-strands with the subsequent α-helices. Many (βα)8-barrel enzymes contain extensions to this canonical topology, either at the Nor C-termini of the sequence, or in loop segments (Pujadas and Palau, 1999). The evolution of the versatile (βα)8-barrel fold has been Biol. Chem., Vol. 382, pp.1315 – 1320, September 2001 · Copyright © by Walter de Gruyter · Berlin · New York