Glimmers in the midnight zone: characterization of aligned identical
residues in sequence-dissimilar proteins sharing a common fold.
In the 8th International Conference on Intelligent Systems for Molecular Biology (ISMB 2000).
Postscript version,
PDF version.
Abstract
Sequence comparison of proteins that adopt the same fold has revealed a large degree of sequence
variation. There are many pairs of structurally similar proteins with only a very low percentage of
identical residues at structurally aligned positions. It is not clear whether these few identical residues
have been conserved just by coincidence, or due to their structural and/or functional role The
current study focuses on characterization of STructurally Aligned Identical ResidueS (STAIRS) in a
data set of protein pairs that are structurally similar but sequentially dissimilar. The conservation
pattern of the residues at structurally aligned positions has been characterized within the protein
families of the two pair members, and mutually highly and weakly conserved positions of STAIRS
could be identified About 40% of the STAIRS are only moderately conserved, suggesting that their
maintenance may have been coincidental. The mutually highly conserved STAIRS show distinct
features that are associated with protein structure and function: a relatively high fraction of these
STAIRS are buried within their protein structures. Glycine, cysteine, histidine, and tryptophan are
significantly over-represented among the mutually conserved STAIRS. A detailed survey of these
STAIRS reveals residue-specific roles in the determination of the protein's structure and function.