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Invariant glycines and prolines flanking in loops the strand β2 of various (α/β) 8 ‐barrel enzymes: A hidden homology?
Author(s) -
Janeček Stefan
Publication year - 1996
Publication title -
protein science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.353
H-Index - 175
eISSN - 1469-896X
pISSN - 0961-8368
DOI - 10.1002/pro.5560050615
Subject(s) - homology (biology) , conserved sequence , biology , sequence alignment , genetics , homology modeling , multiple sequence alignment , structural alignment , computational biology , peptide sequence , enzyme , amino acid , biochemistry , gene
The question of parallel (α/β) 8 ‐barrel fold evolution remains unclear, owing mainly to the lack of sequence homology throughout the amino acid sequences of (α/β) 8 ‐barrel enzymes. The “classical” approaches used in the search for homologies among (α/β) 8 ‐barrels (e.g., production of structurally based alignments) have yielded alignments perfect from the structural point of view, but the approaches have been unable to reveal the homologies. These are proposed to be “hidden” in (α/β) 8 ‐barrel enzymes. The term “hidden homology” means that the alignment of sequence stretches proposed to be homologous need not be structurally fully satisfactory. This is due to the very long evolutionary history of all (α/β) 8 ‐barrels. This work identifies so‐called hidden homology around the strand 02 that is flanked by loops containing invariant glycines and prolines in 17 different (α/β) 8 ‐barrel enzymes, i.e., roughly in half of all currently known (α/β) 8 ‐barrel proteins. The search was based on the idea that a conserved sequence region of an (α/β) 8 ‐barrel enzyme should be more or less conserved also in the equivalent part of the structure of the other enzymes with this folding motif, given their mutual evolutionary relatedness. For this purpose, the sequence region around the well‐conserved second β‐strand of α‐amylase flanked by the invariant glycine and proline (56_GFTAIWITP, Aspergillus oryzae α ‐amylase numbering), was used as the sequence‐structural template. The proposal that the second β‐strand of (α/β) 8 ‐barrel fold is important from the evolutionary point of view is strongly supported by the increasing trend of the observed β2‐strand structural similarity for the pairs of (α/β) 8 ‐barrel enzymes: α‐amylase and the α‐subunit of tryptophan synthase, α‐amylase and mandelate racemase, and α‐amylase and cyclodextrin glycosyltransferase. This trend is also in agreement with the existing evolutionary division of the entire family of (α/β) 8 ‐barrel proteins.