A Novel Aminopeptidase with Highest Preference for Lysine

Hui, Maria; Hui, Koon-Sea

doi:10.1007/s11064-005-9234-9

Cited by 4 publications

(4 citation statements)

References 19 publications

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“…This is further supported by the detection of residual activity against H-Lys-Ala-pNA in intact cells following treatment with selective DP2 inhibitors (64,65). As a number of aminopeptidases are capable of cleaving N-terminal Lys and Ala residues (66)(67)(68)(69) it is reasonable to suggest that one or more aminopeptidases may be responsible for the cleavage of Lys, then Ala, from the synthetic substrate and thus release of pNA for colorimetric detection in the DP2 enzyme assay.…”

Section: Discussionmentioning

confidence: 89%

Expression profiling of dipeptidyl peptidase 8 and 9 in breast and ovarian carcinoma cell lines

Wilson

Abbott

2012

International Journal of Oncology

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Abstract. Proteases, particularly serine proteases like dipeptidyl peptidase 4 (DP4) and fibroblast activation protein (FAP), play an important role in cancer invasion and angiogenesis. Aberrant expression of DP4 and FAP is associated with numerous cancers, including breast and epithelial ovarian carcinoma. We investigated the mRNA levels, protein expression and enzyme activity of the structural homologs DP8 and DP9, in addition to DP4 and FAP, in three breast carcinoma (MDA-MB-231, MDA-MB-453, MCF-7), three epithelial ovarian carcinoma (EOC) (OVCA-432, OVCA-429, SKOV3), 293T and HeLa cell lines. In addition, DP2 and prolyl endopeptidase (PEP) mRNA and enzyme levels were measured and compared in each cell line. Ubiquitous but differential expression of DP8 and DP9 mRNA and protein was observed across all cell lines. Relative to EOC, DP8 protein was lower in the breast carcinoma cell lines (p= 0.057), suggesting that DP8 may play differing roles in different cancer cell types. A strong, negative, non-reciprocal relationship was identified between DP9 protein and DP4 mRNA (r=-0.903, p=0.002) and protein (r=-0.810, p=0.015). This suggests that DP4 expression plays an important role in the post-transcriptional regulation of DP9 in breast and ovarian cancer cell lines. Overall, this study suggests a potential role for DP8 and DP9 in breast and ovarian cancer and further investigations in this area are required. IntroductionBreast and ovarian cancer are two of the most common and lethal cancers affecting women worldwide. Estimates rank breast cancer as being the number one cause of new cancer cases (1,383,000 cases, 22.9%) and cancer related deaths (458,000 deaths, 13.7%) in women worldwide in 2008. Ovarian cancer was ranked as the seventh cause of new cancer cases (225,000 cases, 3.7%) and cancer related deaths (140,000 deaths, 4.2%) in women worldwide in the same year (1). Among gynecological malignancies, epithelial ovarian carcinoma (EOC) is the most lethal to women in the world, accounting for approximately 90% of all tumors affecting the ovaries (2). Mortality from breast cancer often results from distant metastatic spread to lung, bone and lymph node tissue while diagnosis of EOC typically occurs in the late stages of disease after its spread into the peritoneal cavity or other distant sites (2), thus making it difficult for effective treatment to be administered. Although a number of risk factors for the development of breast and ovarian cancer have been identified the exact origin and pathogenesis of disease is still poorly understood (3,4). Increasing our knowledge about the fundamental biology of these diseases is needed for the development of improved diagnostic, prognostic and therapeutic interventions at all stages of disease.Enzymatic members of the DP4-like gene family, DP4, FAP, DP8 and DP9, share the rare ability to cleave N-terminal dipeptides at post-proline bonds in the penultimate position and play an important role in the biological processing of the N-termini of peptides such as chemokines, glu...

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Section: Discussionmentioning

confidence: 89%

Expression profiling of dipeptidyl peptidase 8 and 9 in breast and ovarian carcinoma cell lines

Wilson

Abbott

2012

International Journal of Oncology

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“…The tiny peaks of the basic lysine aminopeptidase (KAP) and the arginine aminopeptidase (RAP; aminopeptidase B) were eluted before Peak I. The KAP was eluted with a much lower concentration of NaCl at 0.11 M and the RAP at 0.15 M (Hui and Hui, 2006). The dimensions of Peak I, Peak II, and Peak III changed when assayed with various amino acyl βNA substrates.…”

Section: Resultsmentioning

confidence: 99%

A new type of neuron-specific aminopeptidase NAP-2 in rat brain synaptosomes

Hui

2008

Neurochemistry International

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A novel neutral aminopeptidase (NAP-2)1 was found exclusively in the rat central nervous system (CNS). It was separated from the ubiquitous puromycin-sensitive aminopeptidase (PSA) and the neuron-specific aminopeptidase (NAP) by an automated FPLC-aminopeptidase analyzer. The activity of the neuronal aminopeptidase enriched in the synaptosomes is different from NAP and PSA in distribution and during brain development. The enzyme was purified 2,230-fold to apparent homogeneity from rat brain cytosol with 4% recovery by ammonium sulfate fractionation, followed by column chromatography successively on Phenyl-Sepharose, Q-Sepharose, Sephadex G-200, and Mono Q. The single-chain enzyme with a molecular mass of 110 kDa has an optimal pH of 7.0 and a pI of 5.6. It splits β-naphthylamides of amino acid with aliphatic, polar uncharged, positively charged, and aromatic side chain. Leucyl β-naphthylamide (Leu βNA) is the best substrate with the highest hydrolytic coefficiency followed by Met βNA = Arg βNA = Lys βNA > Ala βNA > Tyr βNA > Phe βNA. The cysteine-, metallo-, glyco-aminopeptidase releases the N-terminal Tyr from Leu-enkephalin with a K m 82 μM and a k cat of 1.08 s −1 , and Met-enkephalin with a K m of 106 μM and a k cat of 2.6 s −1 . The puromycin-sensitive enzyme is most susceptible to amastatin with an IC 50 of 0.05 μM. The data indicate that the enzyme is a new type of neuron-specific aminopeptidase found in rodent. Its possible function in neuron growth, neurodegeneration, and carcinomas is discussed.

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“…Two zinc dependent metalloenzymes [15][16][17][18], leukotriene (LT)-A4 hydrolase (LT-A4-H) (EC 3.3.2.6) and basic aminopeptidase (APB) (EC 3.4.11.6), seem to exhibit concomitant hydrolytic activities on L-arginyl-β-naphthylamide (ArgNA) and on LT-A4 [18][19][20][21][22][23]. EC 3.4.11.6 preferentially hydrolyzes basic residues (Arg and Lys) of peptides [17,18,24,25], being ArgNA its preferential synthetic substrate [26]. This enzyme is structurally similar to EC 3.3.2.6 (33% identity and 48% similarity) and it has also been reported to exhibit LT-A4-H activity [16,17,27].…”

Section: Introductionmentioning

confidence: 99%

Leukotriene-A4-Hydrolase and Basic Aminopeptidase Activities Are Related with Collagen-Induced Arthritis in a Compartment-Dependent Manner

Mendes¹,

Silveira²

2013

OJRA

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Objective: Previous study demonstrated the involvement of basic aminopeptidase (APB) activity in the development of collagen-induced arthritis (CIA). Two zinc dependent metalloenzymes (EC 3.4.11.6 and EC 3.3.2.6) are known to exhibit concomitantly APB and leukotriene-A4-hydrolase (LT-A4-H) activities. Influence of the interrelationship between both activities on arthritic processes, however, is presently uncertain. This study aimed to compare these activities in CIA. Methods: CIA was induced in rats and arthritis was assessed macroscopically. Ultracentrifugation was used to separate soluble (S) and solubilized membrane-bound (M) fractions from peripheral blood mononuclear cells (PBMCs) and synovial tissue (ST). Enzyme immunoassay was used to measure LT-A4-H activity, and Real Time Polymerase Chain Reaction was used for evaluating EC 3.4.11.6 and EC 3.3.2.6 gene expressions. Results: The existence of genes for EC 3.3.2.6 and EC 3.4.11.6 was demonstrated in the ST. Compared with control, LT-A4-H activity increased in synovial fluid (SF) and in S-PBMCs of CIA-arthritic and CIA-resistant and in M-ST of CIA-resistant, while it decreased in M-PBMCs of CIA-arthritic and CIA-resistant. In all these locations APB activity remained unchanged or inversely correlated with LT-A4-H activity. Conclusions: LT-A4-H and APB activities in joint-related samples are associated, for the first time, with EC 3.3.2.6 and EC 3.4.11.6 genes, exhibiting a compartment-dependent differential modulation of their specificity, efficiency and/or affinity or an inverse concurrent pattern. Changes in LT-A4-H activity have implications for development or resistance to arthritis in CIA model with a potential to be a diagnostic tool.

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A Novel Aminopeptidase with Highest Preference for Lysine

Cited by 4 publications

References 19 publications

Expression profiling of dipeptidyl peptidase 8 and 9 in breast and ovarian carcinoma cell lines

Expression profiling of dipeptidyl peptidase 8 and 9 in breast and ovarian carcinoma cell lines

A new type of neuron-specific aminopeptidase NAP-2 in rat brain synaptosomes

Leukotriene-A4-Hydrolase and Basic Aminopeptidase Activities Are Related with Collagen-Induced Arthritis in a Compartment-Dependent Manner

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