Cloning, chromosomal sublocalization of the human soluble aminopeptidase P gene (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 related in terms of catalytic specificity to an ectoenzyme, membrane aminopeptidase P (hmAmP), which is largely limited in distribution to endothelia and brush border epithelia. Although both enzymes can degrade oligopeptides having N-terminal Xaa-Pro- moieties, hsAmP and hmAmP are of relatively low sequence homology. Recently, it has been shown that the two enzymes are not products of splice variants of the same gene. How hsAmP relates to hmAmP has clinical significance in that both can inactivate bradykinin, and AmP deficiency states have been described. The hmAmP gene (XPNPEP2) is disposed at chromosome 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 on chromosome 10q25.3. We also show that hsAmP and hmAmP contain homologous blocks of sequence common to members of the "pita bread-fold" protein family, of which Escherichia coli methionine aminopeptidase is the prototype. The prototype is known to contain a proton shuttle and five divalent metal ligands, counterparts of which we identify in the homologous blocks of sequence in both hsAmP and hmAmP and compare to E. coli aminopeptidase.
Sprinkle
T J
TJ
Department of Neurology, Medical College of Georgia and Veterans Administration Medical Center, Augusta 30912, USA. sprinkle@np2.mcg.edu
Caldwell
C
C
Ryan
J W
JW
D000595:Amino Acid Sequence; D000626:Aminopeptidases / Q000235:genetics* / Q000378:metabolism; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D002874:Chromosome Mapping; D002879:Chromosomes, Human, Pair 10 / Q000235:genetics*; D003001:Cloning, Molecular; D017124:Conserved Sequence; D017931:DNA Primers / Q000235:genetics; D004926:Escherichia coli / Q000201:enzymology / Q000235:genetics; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008024:Ligands; D008566:Membranes / Q000201:enzymology; D008670:Metals; D008969:Molecular Sequence Data; D011522:Protons; D017386:Sequence Homology, Amino Acid; D012995:Solubility
D017931:DNA Primers; D008024:Ligands; D008670:Metals; D011522:Protons; D000626:Aminopeptidases; C022750:X-Pro aminopeptidase