Prediction of secondary structure by evolutionary comparison: Application to the α subunit of tryptophan synthase

Abstract

The amino acid sequences of the a subunits of tryptophan synthase from ten different microorganisms were aligned by standard procedures. The alpha helices, beta strands and turns of each sequence were predicted separately by two standard prediction algorithms and averaged at homologous sequence positions. Additional evidence for conserved secondary structure was derived from profiles of average hydropathy and chain flexibility values, leading to a joint prediction. There is good agreement between (1) predicted beta strands, maximal hydropathy and minimal flexibility, and (2) predicted loops, great chain flexibility, and protein segments that accept insertions of various lengths in individual sequences. The a subunit is predicted to have eight repeated beta-loop-alpha-loop motifs with an extra N-terminal alpha helix and an intercalated segment of highly conserved residues. This pattern suggests that the territory structure of the a subunit is an eightfold alpha/beta barrel. The distribution of conserved amino acid residues and published data on limited proteolysis, chemical modification, and mutagenesis are consistent with the alpha/beta barrel structure. Both the active site of the a subunit and the combining site for the beta 2 subunit are at the end of the barrel formed by the carboxyl-termini of the beta strands.

Alignment and structure prediction of divergent protein families: periplasmic and outer membrane proteins of bacterial efflux pumps

“…This idea is used by the PHD program and other secondary structure prediction methods (Barton et al, 1991;Crawford et al, 1987;Levin et al, 1993;Salamov & Solovyev, 1995;Zvelebil et al, 1987). To extend this principle beyond secondary structure prediction, the MAPF program was developed.…”

An Evolutionary Trace Method Defines Binding Surfaces Common to Protein Families

“…These observations imply that evolutionarily related sequences can be compared with one another to extract structural and functional data (Baldwin, 1993;Benner, 1989;Livingstone & Barton, 1993;Sternberg & Cohen, 1982;Zvelebil & Sternberg, 1988). Indeed, useful strategies for protein secondary and tertiary structure prediction based on sequence alignment have been proposed (Barton, 1990;Benner et al, 1994;Crawford et al, 1987;Sander & Schneider, 1991).…”

Structural design and molecular evolution of a cytokine receptor superfamily.

“…Consensus f-strand patterns defined the likely components ofthe core domain fold. This approach has been successful in modeling the secondary and tertiary structures of viral proteases (14,16) and the a subunit of tryptophan synthase (18).…”