The Aeromonas proteolytica aminopeptidase
(AMP), Pseudomonas sp. (RS-16) carboxypeptidase
G2 (CPG2), and Streptomyces griseus aminopeptidase
(SGAP) are zinc dependent proteolytic enzymes with cocatalytic
zinc ion centers and a conserved aminopeptidase fold. A
BLAST search with the sequence of the solved AMP structure
indicated that a similar domain could be found in prostate-specific
membrane antigen (PSMA) and the transferrin receptor (TfR).
When the PSMA or TfR sequence was input into the THREADER
program, the top structural matches were SGAP and AMP confirming
that these are structurally conserved domains. Optimal
sequence alignment of PSMA and TfR using the known three-dimensional
structures of AMP, CPG2, and SGAP shows that the critical
amino acids involved in forming the catalytic pocket are
conserved in PSMA but absent in the TfR. The specificity
pocket in AMP is formed from four aromatic side chains
and the equivalent region in CPG2/PSMA has a changed sequence
pattern. Since CPG2 and PSMA are folate hydrolases, the
changed specificity pocket leaves space to accommodate
the large pteroate moiety of folic acid. In contrast, no
enzyme function has been ascribed to the TfR.