Disease relevance of Rnpep

• The data obtained suggest that Arginine-aminopeptidase could perform processing of angiotensin peptides in the myocardium and participate in processes regulated by angiotensins such as fibrosis [1].
• Inhibitors of aminopeptidase B suppress the development of hypertension in spontaneously hypertensive rats [2].
• The Ap-B cDNA was constructed from extracted rat testes total RNA and introduced into the pBAC1 baculovirus transfer vector to generate recombinant baculoviruses. rAp-B expression, with or without COOH-hexahistidine tag, was tested in two different insect cell hosts (Sf9 and H5) [3].

High impact information on Rnpep

• Aminopeptidase B from the rat testis is a bifunctional enzyme structurally related to leukotriene-A4 hydrolase [4].
• It exhibits 33% identity and 48% similarity with leukotriene-A4 hydrolase, a relation further supported by the capacity of Ap-B to hydrolyze leukotriene A4 [4].
• Ap-B and its mRNA were detected in the germ line and in the Sertoli and peritubular cells of the seminiferous tubules [4].
• In the present work, by using oligonucleotides selected on the basis of partial amino acid microsequences of pure Ap-B and PCR techniques, the nucleotide sequence of a 2.2-kb cDNA was obtained [4].
• We isolated, by immunological screening of a Uni-ZAP XR cDNA library constructed from rat liver mRNAs, a cDNA clone with 2212 base pairs encoding aminopeptidase B (EC 3.4.11.6) [5].

Biological context of Rnpep

• From sequence-homology searches, Ap B is known to be closely related to leukotriene (LT)-A4 hydrolase (EC 3.3.2.6) [6].
• Aminopeptidase B (Ap B; EC 3.4.11.6) is a zinc-binding protein that contains the consensus sequence HEXXHX18E (324-347), conserved among the M1 family of metallopeptidases [6].
• OBJECTIVE: The aim of the present study was to elucidate the presence in rat cardiac fibroblastic cells of arginine-aminopeptidase and its involvement in the hydrolysis of angiotensin peptides [1].
• These results are in agreement with the known substrate specificity of arginine aminopeptidase [7].
• Previous investigations have suggested an important role for cationic residues in determination of toxin activity, and our single-site mutagenesis studies have indicated that isoform discrimination can be partially explained by the unique cationic residues Arg-12 and Lys-49 of anthopleurin B (ApB) [8].

Anatomical context of Rnpep

• Instead, they could be first hydrolyzed by another peptidase in fibroblasts and the product of this hydrolysis could be a substrate for Arginine-aminopeptidase [1].
• However, aminopeptidase B, endopeptidase 24-15, and endopeptidase 24-11 were significantly lower in the VTA than in the nucleus accumbens membrane preparations, while proline endopeptidase was detected in significantly higher amount only in the cytosolic fraction prepared from nucleus accumbens [9].
• Aminopeptidase B-like enzymes in leukocytes [10].
• By immunohistochemistry, the aminopeptidase-B was found to be particularly abundant in the seminiferous tubules at late stages of spermatogenesis and was clearly detected in a restricted area of elongated spermatids [11].
• The metabolism of [125I]angiotensin II (AII, octopeptide) and [125I]angiotensin III (AIII, heptapeptide) was determined in the cerebroventricular compartment following intracerebroventricular (i.c.v.) pretreatment with artificial cerebrospinal fluid (aCSF) or the aminopeptidase B inhibitor, bestatin (BE) [12].

Associations of Rnpep with chemical compounds

• Aminopeptidase B (EC 3.4.11.6) is a Zn(2+)-dependent exopeptidase which selectively removes arginine and/or lysine residues from the NH2-terminus of several peptide substrates including Arg0-Leu-enkephalin, Arg0-Met-enkephalin and Arg-1-Lys0-somatostatin-14 [13].
• Whereas the endoprotease cleaves a single peptide bond, between Glu12 and Arg13 of S-28, the aminopeptidase B-like enzyme removes both Arg13 and Lys14 stepwise from the NH2 terminus of the corresponding COOH-terminal fragment [14].
• It is proposed that S-28 processing involves a divalent cation-sensitive endoprotease that is sensitive to thiol reagents, which cleaves before the Arg-Lys doublet, which is not trypsin-like, and whose action is coupled to an aminopeptidase B-like enzyme [14].
• Inhibition of arginine aminopeptidase by bestatin and arphamenine analogues. Evidence for a new mode of binding to aminopeptidases [7].
• CONCLUSIONS: Our data show that chloride-insensitive Arginine-aminopeptidase could contribute to the hydrolysis of all studied angiotensin peptides in concert with other peptidases present in fibroblasts [1].

Other interactions of Rnpep

• We concluded that ACE and the kidney are important to the metabolism of circulating kinins while carboxypeptidase N, neutral endopeptidase 24.11 and aminopeptidase B are not [15].
• Its properties, such as its subcellular localization, substrate specificity, pH optimum, and molecular weight, distinguish it from leucine aminopeptidase, aminopeptidase A, aminopeptidase B, aminopeptidase M, and the soluble aminopeptidase for enkephalin degradation [16].
• Aminopeptidase-B in the rat testes: isolation, functional properties and cellular localization in the seminiferous tubules [11].
• Complementary analyses included assays of lysosomal (cathepsins B, D, H, and L and diaminopeptidases I and II) and cytoplasmic proteases (alanyl aminopeptidase, arginyl aminopeptidase, leucyl aminopeptidase, diaminopeptidase IV, tripeptidyl aminopeptidase, and proline endopeptidase) [17].
• The subcellular localization of both enzymes supports the involvement of aminopeptidase B in processing events associated with the secretory pathway but led to new hypothesis on the possible physiological role(s) of NRD convertase [18].

Analytical, diagnostic and therapeutic context of Rnpep

• Molecular cloning and expression of rat liver aminopeptidase B [5].
• Immunoblottings were performed with antibodies to aminopeptidase B and Glyceraldehyde-3-phosphate dehydrogenase [1].
• RT-PCR and in situ hybridization were used to detect expression of Ap-B mRNA and activity tests, Western blotting and immunofluorescence microscopy were performed to identify and localize the enzyme in the rat retina [19].

References