Reaction of Neprilysin (Neutral Endopeptidase) and Thermolysin with Cyclic Peptides

Vijayaragahaven, Jayanthi; Tucker, Mark A.; Fehrentz, Jean‐Alain; Isbell, D.; Hersh, Louis B.

doi:10.1006/abbi.1995.1481

Cited by 4 publications

(3 citation statements)

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“…It seems therefore that specific structures in proteases are needed to catalyze degradation of microcystin LR. In previous studies employing neprilysin, it is believed that small cyclic peptides have poor flexibility and are difficult to fit into the enzyme pocket for reaction [20]. Since microcystin LR is also a small cyclic peptide (seven amino acids), it would be difficult to degrade by either enzymatic or physico‐chemical factors.…”

Section: Discussionmentioning

confidence: 99%

Detection and sequencing of the microcystin LR-degrading gene,mlrA, from new bacteria isolated from Japanese lakes

Saito

Okano

Park

et al. 2003

FEMS Microbiology Letters

137

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AbstractmlrA is the only microcystin-degrading gene detected in Sphingomonas sp. MJ-PV. The gene has an extremely rare nucleotide sequence and homologous genes have not yet been discovered in the DNA database. We discovered the existence of a gene homologous to mlrA in new microcystin-degrading bacteria, MD-1 and Y2. These strains possessed mlrA homologues, and the identities of the genes of MD-1 and Y2 with the corresponding MJ-PV exceeded 98% and 84%, respectively. On the other hand, the mlrA gene was not detected in laboratory strains of the closely related Sphingomonas spp. strains employing hemi-nested polymerase chain reaction detection using two primer sets. Although the microcystin-degrading bacteria were closely related strains, they did not cluster together as the same species. We can conclude that the mlrA gene is conserved in three different bacterial species, and it is unique to microcystin degraders but not to the genus Sphingomonas.

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Section: Discussionmentioning

confidence: 99%

Detection and sequencing of the microcystin LR-degrading gene,mlrA, from new bacteria isolated from Japanese lakes

Saito

Okano

Park

et al. 2003

FEMS Microbiology Letters

137

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“…Peptides were detected and quantified by absorbance at 215 nm. K inetics were analyzed as we described previously (Vijayaragahaven et al, 1995); Kcat values were determined from the time required for plasmin to reduce A␤ levels by 50%. The identity of the A␤ degradation fragments was determined by using matrix-assisted laser desorption ionization time-of-flight mass spectrometry (C iphergen Biosystems, Palo Alto, CA) to analyze HPLC -purified A␤ fragments.…”

Section: Methodsmentioning

confidence: 99%

The Plasmin System Is Induced by and Degrades Amyloid-β Aggregates

et al. 2000

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Amyloid-beta (Abeta) appears critical to Alzheimer's disease. To clarify possible mechanisms of Abeta action, we have quantified Abeta-induced gene expression in vitro by using Abeta-treated primary cortical neuronal cultures and in vivo by using mice transgenic for the Abeta precursor (AbetaP). Here, we report that aggregated, but not nonaggregated, Abeta increases the level of the mRNAs encoding tissue plasminogen activator (tPA) and urokinase-type plasminogen activator (uPA). Moreover, tPA and uPA were also upregulated in aged AbetaP overexpressing mice. Because others have reported that Abeta aggregates can substitute for fibrin aggregates in activating tPA post-translationally, the result of tPA induction by Abeta would be cleavage of plasminogen to the active protease plasmin. To gain insights into the possible actions of plasmin, we evaluated the hypotheses that tPA and plasmin may mediate Abeta in vitro toxicity or, alternatively, that plasmin activation may lead to Abeta degradation. In evaluating these conflicting hypotheses, we found that purified plasmin degrades Abeta with physiologically relevant efficiency, i.e., approximately 1/10th the rate of plasmin on fibrin. Mass spectral analyses show that plasmin cleaves Abeta at multiple sites. Electron microscopy confirms indirect assays suggesting that plasmin degrades Abeta fibrils. Moreover, exogenously added plasmin blocks Abeta neurotoxicity. In summation, we interpret these results as consistent with the possibility that the plasmin pathway is induced by aggregated Abeta, which can lead to Abeta degradation and inhibition of Abeta actions.

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“…These differences may have been due to the increase in structural flexibility of somatostatin, the 12-membered cyclic peptide (Cys 3 -Cys 14 ) compared with oxytocin and vasopressin, and the sixmembered cyclic peptide (Cys 1 -Cys 6 ). This has also been described by Vijayaragahaven et al, who have shown that the six-membered small peptide is not hydrolyzed by mammalian NEP (neprilysin) and bacterial NEP (thermolysin), whereas the rate of substrate hydrolysis increases with increasing chain length [20].…”

Section: Degradation Ratementioning

confidence: 57%

Microbial degradation of physiologically active peptides by strain B-9

et al. 2011

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The reaction of some physiologically active peptides with bacterial strain B-9 has been investigated. Bradykinin, β-endorphin, and [Leu(5)]enkephalin were quickly degraded, with half-lives of <5 min. Somatostatin, substance P, and angiotensin I were degraded relatively smoothly, with half-lives of 10 min to 1 h, whereas oxytocin and insulin were slowly degraded, with half-lives of 1 and 4 days, respectively. Vasopressin was barely degraded, with a half-life of >7 days. Linearized vasopressin, prepared by the reductive cleavage of the disulfide bond followed by alkylation with iodoacetamide, was degraded significantly faster than intact vasopressin, with a half-life of 2.5 h. A loop formed by disulfide bond formation was regarded as one of the degradation-resistant factors. Hydrolysis of the peptides in this study took place through cleavage of various peptide bonds, and the strain B-9 may bear similarities to the neutral endopeptidase in terms of its broad selectivity.

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Reaction of Neprilysin (Neutral Endopeptidase) and Thermolysin with Cyclic Peptides

Cited by 4 publications

References 0 publications

Detection and sequencing of the microcystin LR-degrading gene,mlrA, from new bacteria isolated from Japanese lakes

Detection and sequencing of the microcystin LR-degrading gene,mlrA, from new bacteria isolated from Japanese lakes

The Plasmin System Is Induced by and Degrades Amyloid-β Aggregates

Microbial degradation of physiologically active peptides by strain B-9

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