Ce. Sansom et al., STRUCTURAL-ANALYSIS AND CLASSIFICATION OF LIPOCALINS AND RELATED PROTEINS USING A PROFILE-SEARCH METHOD, Biochimica et biophysica acta. Protein structure and molecular enzymology, 1208(2), 1994, pp. 247-255
A three-dimensional profile method of detecting amino-acid sequences c
ompatible with the tertiary structure of any protein has been applied
to the lipocalin family of 8-stranded beta-barrels. Profiles derived f
rom six well-resolved lipocalin crystal structures were used to search
a comprehensive, non-redundant protein sequence database. Each profil
e identified a sub-group of lipocalin sequences although no single pro
file was sufficient to identify the whole family. The alpha-1-acid gly
coprotein sub-family was not identified by any lipocalin profile, indi
cating that known sequence differences in otherwise well conserved reg
ions of these proteins may be reflected in structural differences. The
predicted similarity between the beta-lactoglobulin and alpha-2u-glob
ulin structures was much more marked than the similarity between their
sequences, and alpha-1-microglobulin sequences were found to be compa
tible with the structure of epididymal retinoic acid binding protein w
hich has an additional long C-terminal helix. Proteins of unknown stru
cture which were predicted to be compatible with the lipocalin fold in
clude a human mucin. In cases where a large protein family of low over
all sequence similarity contains a small number of known structures, t
his technique can be useful in determining or confirming subtle struct
ural relationships between family members.