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Literature summary for 3.4.24.11 extracted from

  • Burrell, M.; Henderson, S.J.; Ravnefjord, A.; Schweikart, F.; Fowler, S.B.; Witt, S.; Hansson, K.M.; Webster, C.I.
    Neprilysin inhibits coagulation through proteolytic inactivation of fibrinogen (2016), PLoS ONE, 11, e0158114 .
    View publication on PubMedView publication on EuropePMC
Search for more literature for 3.4.24.11

Cloned(Commentary)

Cloned (Comment) Organism
recombinant expression of wild-type and mutant C-terminally human serum albumin-fused extracellular domains of human NEP (amino acids 52-749) in CHO cells Homo sapiens

Protein Variants

Protein Variants Comment Organism
E584V site-directed mutagenesis, inactive mutant, has no effects on prothrombin time (PT) and activated partial thromboplastin time (APTT) in rats and monkeys Homo sapiens
G399V/G714K site-directed mutagenesis, the engineered NEP, HSA-NEPv G399V/G714K, has a potential as therapeutic for Alzheimer disease but in pre-clinical safety testing, this variant increases prothrombin time (PT) and activated partial thromboplastin time (APTT) measured in cynomolgus monkeys and rats dosed with a human serum albumin fusion with an engineered variant of NEP as well as in control plasma spiked with wild-type or mutant enzyme. Wild-type HSA-NEP and mutant HSA-NEPv impair coagulation, increasing PT and APTT in plasma samples and abolishing fibrin formation from fibrinogen. This effect is mediated through cleavage of the N-termini of the Aalpha- and Bbeta-chains of fibrinogen thereby significantly impairing initiation of fibrin formation by thrombin. The effects on PT and APTT are broadly similar in male and female rats although the effect on APTT is less clear cut in females Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
fibrinogen + H2O Homo sapiens inactivation, mechanism of NEP-mediated inactivation of fibrinogen through cleavage of the N-termini of the Aalpha- and Bbeta-chains of fibrinogen thereby significantly impairing initiation of fibrin formation by thrombin, overview fibrin + ?
-
 ?

Organism

Organism UniProt Comment Textmining
Homo sapiens P08473
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-

Purification (Commentary)

Purification (Comment) Organism
recombinant wild-type and mutant C-terminally human serum albumin-fused extracellular domains of human NEP (amino acids 52-749) from CHO cells by affinity chromatography Homo sapiens

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
fibrinogen + H2O inactivation, mechanism of NEP-mediated inactivation of fibrinogen through cleavage of the N-termini of the Aalpha- and Bbeta-chains of fibrinogen thereby significantly impairing initiation of fibrin formation by thrombin, overview Homo sapiens fibrin + ?
-
 ?
fibrinogen + H2O fibrinogen from human and rat blood plasma, inactivation Homo sapiens fibrin + ?
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 ?

Synonyms

Synonyms Comment Organism
NEP
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 Homo sapiens

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
37
-
 assay at Homo sapiens

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
7.4
-
 assay at Homo sapiens

General Information

General Information Comment Organism
physiological function neprilysin inhibits coagulation through proteolytic inactivation of fibrinogen. The enzyme may have a role in regulating fibrin formation. Wild-type HSA-NEP and mutant HSA-NEPv impair coagulation, increasing prothrombin time (PT) and activated partial thromboplastin time (APTT) in plasma samples and abolishing fibrin formation from fibrinogen. This effect is mediated through cleavage of the N-termini of the Aalpha- and Bbeta-chains of fibrinogen thereby significantly impairing initiation of fibrin formation by thrombin Homo sapiens