Characterization of prolidase I and II from erythrocytes of a control, a patient with prolidase deficiency and her mother

Ohhashi, Toshitaka; Ohno, Takashi; Arata, Jirô; Sugahara, Kazunobu; Kodama, Hiroyuki

doi:10.1016/0009-8981(90)90256-r

Cited by 19 publications

(12 citation statements)

References 13 publications

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“…However, both enzymes showed activity when Met-Pro was used as the substrate. Similar results were seen in the isolation of PD I and PD II from human erythrocytes (17,18). As shown in Figure 1B, the antibodies raised against human prolidase reacted with rat PD I and PD II and were substantially identical with respect to enzyme activity.…”

Section: Resultssupporting

confidence: 83%

“…We have also purified PD I and PD II from normal human erythrocytes, and found that the two isolated isoforms of prolidase differed in molecular mass (PD I, 56 kD, and PD II, 95 kD, in SDS-PAGE), response to manganese, substrate specificity, and heat stability (17,18). Moreover, prolidase activity is indeed present in patients with prolidase deficiency, and enzymatic properties of the patient's prolidase are essentially the same as those of PD II (19).…”

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confidence: 99%

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Prolidase Isoenzymes in the Rat: Their Organ Distribution, Developmental Change and Specific Inhibitors

et al. 2007

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Lack of prolidase I (PD I) leads to prolidase deficiency, a disease characterized by intractable skin lesions, recurrent respiratory infections, and mental retardation. The present study was undertaken to characterize and determine the physiologic roles of different prolidase isoenzymes. Two isoforms of prolidase were isolated from rat kidney. PD I showed higher activity against serylproline and alanyl-proline, whereas PD II was active especially against methionyl-proline. PD I was highly concentrated in the small intestine and kidney, whereas PD II was shown not to vary in the organs examined. Expression of PD I and PD II in the small intestine were maximal within 1 wk of birth, and then rapidly declined. The changes of prolidase in the kidney and heart were found to differ slightly. N-benzyloxycarbonyl-L-proline and captopril inhibited PD I dose-dependently, but showed no inhibition of PD II at low concentrations. NiCl 2 inhibited PD II much more effectively than PD I. Our findings suggest that PD I functions by way of an intestinal peptide carrier, which may also be regulated by the uptake of various iminodipeptides. Similarly, age-related alterations of prolidase isoenzymes suggest that intestinal PD II also participates in absorption of proline and other amino acids early in life.

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Section: Resultssupporting

confidence: 83%

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confidence: 99%

Prolidase Isoenzymes in the Rat: Their Organ Distribution, Developmental Change and Specific Inhibitors

et al. 2007

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“…4). In details, the in-frame deletions of exon 5 and exon 7 (Ohhashi et al 1990), located out of the ''pita-bread'' structure, respectively, cause the loss of 15 and 16 amino acids and the synthesis of either an unstable transcript or an unstable protein; the deletion of exons 8-9, falling in the a1 and a2 region of the ''pita-bread'' structure, compromised the stability of the transcript (Forlino et al 2002). Two different mutations at position 184 had been described: R184Z and R184X (Kikuchi et al 2000;Ledoux et al 1996).…”

Section: Discussionmentioning

confidence: 99%

“…This residue corresponds to D97 in E. coli AMPM, a cobalt ligand in the active site. Point mutation 826G>A causing the G278D also is located in the b B region, and 1342G>A causing the G448R both introduce a charged residue in close proximity to the negatively charged active site metalbinding residues D276 and E452 (Ohhashi et al 1990;Ledoux et al 1996). Ledoux et al speculate that the function of these metal-binding residues might be affected by steric or electronic hindrance as a result of these mutations with consequent loss of enzyme activity.…”

Section: Discussionmentioning

confidence: 99%

“…Ledoux et al speculate that the function of these metal-binding residues might be affected by steric or electronic hindrance as a result of these mutations with consequent loss of enzyme activity. The E452/453del removes one of the metal binding site (Ohhashi et al 1990). The deletion of À774 bp that eliminates all exon 14 causes the loss of b' B and b' C regions according to the model of Bazan et al and also includes the loss of G448.…”

Section: Discussionmentioning

confidence: 99%

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Characterization of a new PEPD allele causing prolidase deficiency in two unrelated patients: natural-occurrent mutations as a tool to investigate structure–function relationship

et al. 2004

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Prolidase deficiency (PD) is a rare autosomal recessive disorder characterized mainly by skin lesions of the legs and feet, mental retardation, and respiratory infections. Mutations at the PEPD locus, located on chromosome 19, are responsible for this disease. We identified a new PEPD allele in two unrelated Portuguese PD patients by analyses of reverse transcribed PCR-amplified cDNA. We used SSCP analysis of seven overlapping fragments spanning the entire coding region of the gene and detected abnormal SSCP bands in two of them: PD3 (nt 425-743) and PD4 (nt 661-973). Direct sequencing of the mutant cDNA and genomic DNA revealed a new homozygous 3-bp deletion (Y231del) in both cases. Transient expression in PD fibroblasts of wild-type and mutant prolidase cDNA confirmed reduced activity of the construct carrying the 3-bp deletion. The mutation results in a loss of prolidase activity in skin fibroblasts. Intracellular accumulation of Gly-Pro dipeptide in long-term cultured fibroblasts was detected by capillary electrophoresis. The mutation falls in the a2 domain of the ''pita bread'' structure proposed for E. coli and human prolidase by Bazan et al. on the bases of their sequence homology with E. coli methionine aminopeptidase. Taking into account the effects of the described mutations on stability and activity of the enzyme, we propose the identification of three different functional regions.

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Prolidase is a critical enzyme for complete gliadin digestion in Tenebrio molitor larvae

Tereshchenkova

Goptar

Zhuzhikov

et al. 2017

Arch Insect Biochem Physiol

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Prolidase is a proline-specific metallopeptidase that cleaves imidodipeptides with C-terminal Pro residue. Prolidase was purified and characterized from the Tenebrio molitor larval midgut. The enzyme was localized in the soluble fraction of posterior midgut tissues, corresponding to a predicted cytoplasmic localization of prolidase according to the structure of the mRNA transcript. Expression of genes encoding prolidase and the major digestive proline-specific peptidase (PSP)-dipeptidyl peptidase 4-were similar. The pH optimum of T. molitor prolidase was 7.5, and the enzyme was inhibited by Z-Pro, indicating that it belongs to type I prolidases. In mammals, prolidase is particularly important in the catabolism of a proline-rich protein-collagen. We propose that T. molitor larval prolidase is a critical enzyme for the final stages of digestion of dietary proline-rich gliadins, providing hydrolysis of imidodipeptides in the cytoplasm of midgut epithelial cells. We propose that the products of hydrolysis are absorbed from the luminal contents by peptide transporters, which we have annotated in the T. molitor larval gut transcriptome. The origin of prolidase substrates in the insect midgut is discussed in the context of overall success of grain feeding insects.

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Characterization of prolidase I and II from erythrocytes of a control, a patient with prolidase deficiency and her mother

Cited by 19 publications

References 13 publications

Prolidase Isoenzymes in the Rat: Their Organ Distribution, Developmental Change and Specific Inhibitors

Prolidase Isoenzymes in the Rat: Their Organ Distribution, Developmental Change and Specific Inhibitors

Characterization of a new PEPD allele causing prolidase deficiency in two unrelated patients: natural-occurrent mutations as a tool to investigate structure–function relationship

Prolidase is a critical enzyme for complete gliadin digestion in Tenebrio molitor larvae

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