A method to search for similar protein local structures at ligand-binding sites and its application to adenine recognition |
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Authors: | Nobuo Kobayashi N Go |
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Institution: | (1) Department of Chemistry, Graduate School of Science, Kyoto University, Kitashirakawa-Oiwakecho, Kyoto 606-01, Japan (Fax 81-75-711-6083; e-mail: go@qchem.kuchem.kyoto-u.ac.jp), JP |
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Abstract: | We have developed a method of searching for similar spatial arrangements of atoms around a given chemical moiety in proteins
that bind a common ligand. The first step in this method is to consider a set of atoms that closely surround a given chemical
moiety. Then, to compare the spatial arrangements of such surrounding atoms in different proteins, they are translated and
rotated so that the chemical moieties are superposed on each other. Spatial arrangements of surrounding atoms in a pair of
proteins are judged to be similar, when there are many corresponding atoms occupying similar spatial positions. Because the
method focuses on the arrangements of surrounding atoms, it can detect structural similarities of binding sites in proteins
that are dissimilar in their amino acid sequences or in their chain folds. We have applied this method to identify modes of
nucleotide base recognition by proteins. An all-against-all comparison of the arrangements of atoms surrounding adenine moieties
revealed an unexpected structural similarity between protein kinases, cAMP-dependent protein kinase (cAPK), and casein kinase-1
(CK1), and D-Ala:D-Ala ligase (DD-ligase) at their adenine-binding sites, despite a lack of similarity in their chain folds.
The similar local structure consists of a four-residue segment and three sequentially separated residues. In particular the
four-residue segments of these enzymes were found to have nearly identical conformations in their backbone parts, which are
involved in the recognition of adenine. This common local structure was also found in substrate-free three-dimensional structures
of other proteins that are similar to DD-ligase in the chain fold and of other protein kinases. As the proteins with different
folds were found to share a common local structure, these proteins seem to constitute a remarkable example of convergent evolution
for the same recognition mechanism.
Received: 9 December 1996 / Accepted: 7 February 1997 |
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Keywords: | Molecular recognition Search for similar arrangements of atoms Adenine recognition Database search |
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