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Literature summary for 3.4.24.11 extracted from

  • Moss, S.; Subramanian, V.; Acharya, K.R.
    High resolution crystal structure of substrate-free human neprilysin (2018), J. Struct. Biol., 204, 19-25 .
    View publication on PubMed

Cloned(Commentary)

Cloned (Comment) Organism
recombinant expression of the N-terminally His6-tagged extracellular catalytic domain, NEP(Tyr51-Trp749), in Pichia pastoris strain GS115. The cytoplasmic (Gly1-Glu27) and transmembrane (Ile28-Ala50) domains of NEP are absent in the construct Homo sapiens

Crystallization (Commentary)

Crystallization (Comment) Organism
isolated extracellular catalytic domain of human neprilysin, 8 mg/ml protein in 25 mM Tris, 150 mM NaCl, and 2 mM MgCl2, pH 7.5, are mixed 1:1 with crystallisation buffer containing 0.2 M KNO3 and 20% w/v PEG 3350, 18°C, 1 month, X-ray diffracton structure determination and analysis at 1.9 A resolution Homo sapiens

Localization

Localization Comment Organism GeneOntology No. Textmining
membrane neprilysin is a transmembrane M13 zinc metalloprotease Homo sapiens 16020
-

Metals/Ions

Metals/Ions Comment Organism Structure
Zn2+ neprilysin is a transmembrane M13 zinc metalloprotease. The zinc ion is coordinated by conserved residues H583 and H587and additional coordination is provided by E646. The third conserved residue, E584, is involved in the catalytic mechanism and adopts a position above the zinc ion completing coordination sphere Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
amyloid-beta + H2O Homo sapiens
-
?
-
?
bradykinin + H2O Homo sapiens
-
?
-
?
endothelin-1 + H2O Homo sapiens
-
?
-
?
enkephalin + H2O Homo sapiens
-
?
-
?
insulin + H2O Homo sapiens
-
?
-
?
neurotensin + H2O Homo sapiens
-
?
-
?
Substance P + H2O Homo sapiens
-
?
-
?

Organism

Organism UniProt Comment Textmining
Homo sapiens P08473
-
-

Posttranslational Modification

Posttranslational Modification Comment Organism
glycoprotein four sites of N-linked glycosylation have been confirmed at positions N144, N284 and N324 in subdomain 2 and position N627 in subdomain 1 Homo sapiens

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
amyloid-beta + H2O
-
Homo sapiens ?
-
?
bradykinin + H2O
-
Homo sapiens ?
-
?
endothelin-1 + H2O
-
Homo sapiens ?
-
?
enkephalin + H2O
-
Homo sapiens ?
-
?
insulin + H2O
-
Homo sapiens ?
-
?
Mca-RPPGFSAFK-(Dnp) + H2O
-
Homo sapiens ?
-
?
neurotensin + H2O
-
Homo sapiens ?
-
?
Substance P + H2O
-
Homo sapiens ?
-
?

Synonyms

Synonyms Comment Organism
NEP
-
Homo sapiens

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
30
-
assay at Homo sapiens

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
6
-
assay at Homo sapiens

General Information

General Information Comment Organism
additional information the enzyme contains the HEXXH motif. The zinc ion is coordinated by conserved residues H583 and H587 and additional coordination is provided by E646. The third conserved residue, E584, is involved in the catalytic mechanism and adopts a position above the zinc ion completing coordination sphere. Active site flexibility and modelling, overview. Enzyme crystal structure comparisons Homo sapiens
physiological function neprilysin is a transmembrane M13 zinc metalloprotease responsible for the degradation of several biologically active peptides including insulin, enkephalin, substance P, bradykinin, endothelin-1, neurotensin and amyloid-beta Homo sapiens