Divergent Evolution of ()8-Barrel Enzymes

lationship), superfamilies (probable common evolution-ary origin) and folds (Murzin et al., 1995). Proteins are de-fined 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 ox-idoreductases, transferases, hydrolases, lyases or iso-merases (Pujadas and Palau, 1999; Wierenga, 2001). The (βα)8-barrel consists of a core of eight twisted parallel β-strands, the β-barrel, which are connected by eight α-he-lices 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 sub-sequent α-helices. Many (βα)8-barrel enzymes contain extensions to this canonical topology, either at the N- or C-termini of the sequence, or in loop segments (Pujada