A structural homology of the pyridoxal-5'-phosphate (PLP)-dependent enzyme serine hydroxymethyltransferase (SHMT) with aspartate aminotransferase (AAT) is proposed. Although the two sequences are very dissimilar, a reasonable alignment was obtained using the profile analysis method. Sequences of AAT and dialkylglycine decarboxylase (DGD), for which crystal structure data are available, have been aligned on the basis of their structure superposition. A profile was then calculated and SHMT sequence aligned to it. Three of the four residues conserved in all aminotransferases (including the PLP-binding lysine) are matched. A profile search with DGD-AAT-SHMT profile is more selective and sensitive than individual sequence profiles for PLP-dependent enzyme detection. Potential homologies with the eryC1 gene product involved in erythromycin biosynthesis and with amino acid decarboxylases were observed. Homology with AAT will be used as a guideline for planning site-directed mutagenesis experiments on SHMT.