The extracellular regions of PSMA and the transferrin receptor contain an aminopeptidase domain: Implications for drug design

Daruka Mahadevan, José W. Saldanha

Research output: Contribution to journalArticle

33 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2546-2549
Number of pages4
JournalProtein Science
Volume8
Issue number11
DOIs
StatePublished - 1999

Keywords

  • Aminopeptidase
  • Catalytic pocket
  • Folate hydrolase
  • Prostate-specific membrane antigen
  • Specificity pocket
  • Transferrin receptor

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

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