Cloning, chromosomal sublocalization of the human soluble aminopeptidase Pgene (XPNPEP1) to 10q25.3 and conservation of the putative proton shuttle and metal ligand binding sites with XPNPEP2

Human soluble ("cytosolic") aminopeptidase P (hsAmP) is an aminoacylprolyl hydrolase (EC 3.4.11.9) present in all tissues yet examined. hsAmP is relat ed in terms of catalytic specificity to an ectoenzyme, membrane aminopeptid ase P (hmAmP), which is largely limited in distribution to endothelia and b rush border epithelia, Although both enzymes can degrade oligopeptides havi ng N-terminal Xaa-Pro- moieties, hsAmP and hmAmP are of relatively low sequ ence homology. Recently, it has been shown that the two enzymes are not pro ducts of splice variants of the same gene. How hsAmP relates to hmAmP has c linical significance in that both can inactivate bradykinin, and AmP defici ency states have been described. The hmAmP gene (XPNPEP2) is disposed at ch romosome Xq25, a disposition with clear meaning in terms of inheritance of hmAmP deficiencies. To further explore similarities and differences between hsAmP and hmAmP, the present study was begun to determine the chromosomal disposition of the hsAmP gene. Here we show that the gene is sublocalized o n chromosome 10q25.3. We also show that hsAmP and hmAmP contain homologous blocks of sequence common to members of the "pita bread-fold" protein famil y, of which Escherichia coli methionine aminopeptidase is the prototype. Th e prototype is known to contain a proton shuttle and five divalent metal li gands, counterparts of which me identify in the homologous blocks of sequen ce in both hsAmP and hmAmP and compare to E. coli aminopeptidase, (C) 2000 Academic Press.