Extraction of the ligand-related motifs in enzymes

Mikita Suyama (suyama@kuicr.kyoto-u.ac.jp)
Takaaki Nishioka (nishioka@kuicr.kyoto-u.ac.jp)
Jun'ichi Oda

Institute for Chemical Research, Kyoto University
Uji, Kyoto-Fu 611, Japan


To extract the ligand-related motifs from the sequences of enzymes, we have constructed Ligand Chemical Database for Enzyme Reaction that links a chemical compound to amino acid sequences. Among 1,966 ligands registered, 519 chemical compounds were related to 1,488 ligand-linked sequences. Sequence fragments of 10-residue long, commonly found among the ligand-linked sequences for each chemical compound, were defined as ligand-related motifs. Motifs extracted for pyridoxal phosphate were tested against the crystal structures of aspartate aminotransferase complexed with pyridoxal phosphate. Twenty-four motifs among 93 motifs extracted from the enzyme include the residues that make chemical interactions with the bound pyridoxal phosphate. One of the motifs, K-x-x-G-L-x-x-x-R-V, actually participates in the recognition of pyridoxal phosphate in another enzyme, 1-aminocyclopropane-1-carboxylate synthase. The present approach provides the ligand-related motifs and shows great potentials to characterize the unknown genes sequenced by the genome project.