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Neprilysin

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<StructureSection load='1dmt' size='400' side='right' caption='Structure of glycosylated human neprilysin extracellular domain complex with phosphoramidon (PDB entry [[1dmt]])' scene=''>
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<StructureSection load='1dmt' size='400' side='right' caption='Structure of glycosylated human neprilysin extracellular domain complex with phosphoramidon and Zn+2 ion (grey) (PDB entry [[1dmt]])' scene='51/516479/Cv/1'>
== Function ==
== Function ==
'''Neprilysin''' (NEP), also known as '''neutral endopeptidase''', is a Zn-dependent metalloprotease which degrades small secreted peptides like the beta-amyloid peptide, tachykinin, neurotensin and enkephalins.<ref>PMID: 15134871</ref><ref>PMID: 15544569</ref><ref>PMID: 17476590</ref><ref>PMID: 18393807</ref><ref>PMID: 18470479</ref><ref>PMID: 23684647</ref><ref>PMID: 23883611</ref><ref>PMID: 24391587</ref> NEP turns off peptide signaling events at the cell surface. NEP is found in brain tissue and is an integral membrane protein.
'''Neprilysin''' (NEP), also known as '''neutral endopeptidase''', is a Zn-dependent metalloprotease which degrades small secreted peptides like the beta-amyloid peptide, tachykinin, neurotensin and enkephalins.<ref>PMID: 15134871</ref><ref>PMID: 15544569</ref><ref>PMID: 17476590</ref><ref>PMID: 18393807</ref><ref>PMID: 18470479</ref><ref>PMID: 23684647</ref><ref>PMID: 23883611</ref><ref>PMID: 24391587</ref> NEP turns off peptide signaling events at the cell surface. NEP is found in brain tissue and is an integral membrane protein.
== Relevance ==
== Relevance ==
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NEP signaling has also been implicated in cardiovascular disease.<ref>PMID: 21046489</ref> NEP level increases in Alzheimer's disease patients<ref>PMID: 19606063</ref>. NEP inhibitors are tested as analgesics and anti-hypertensive agents.
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NEP signaling has also been implicated in cardiovascular disease.<ref>PMID: 21046489</ref> NEP level increases in Alzheimer's disease patients<ref>PMID: 19606063</ref>. NEP inhibitors like [[Sacubitril]] and [[Sacubitril/valsartan]] are tested as analgesics and anti-hypertensive agents.
== Structural highlights ==
== Structural highlights ==
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A tetrahedrally coordinated Zn atom interacts with the NEP inhibitor and is involved in the catalysis<ref>PMID: 1669592</ref>.
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A <scene name='51/516479/Cv/6'>tetrahedrally coordinated Zn atom interacts with the NEP inhibitor</scene> and is involved in the catalysis<ref>PMID: 10669592</ref>. <scene name='51/516479/Cv/7'>Active site</scene>. Water molecules are shown as red spheres.
==3D structures of neprilysin==
==3D structures of neprilysin==
Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
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[[1dmt]] – hNEP extracellular domain + Zn + phosphoramidon – human<br />
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[[6gid]] - hNEP extracellular domain 52-750 - human<br />
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[[6sh1]] - hNEP extracellular domain (mutant)<br />
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[[6sh2]] - hNEP extracellular domain (mutant) + natriuretic peptide<br />
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[[1dmt]] – hNEP extracellular domain + Zn + phosphoramidon <br />
[[4cth]] - hNEP extracellular domain (mutant) + Zn + phosphoramidon<br />
[[4cth]] - hNEP extracellular domain (mutant) + Zn + phosphoramidon<br />
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[[1r1h]], [[1r1i]], [[1r1j]], [[1y8j]], [[2qpj]], [[2yb9]] - hNEP extracellular domain + Zn + inhibitor<br />
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[[5jmy]] - hNEP extracellular domain + subitril<br />
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[[2yvc]] – NEP cytoplasmic tail + radixin - mouse
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[[1r1h]], [[1r1i]], [[1r1j]], [[1y8j]], [[2qpj]], [[2yb9]], [[6suk]], [[6svy]], [[6thp]], [[6xvp]] - hNEP extracellular domain + Zn + inhibitor<br />
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[[2yvc]] – NEP cytoplasmic tail + radixin - mouse<br />
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[[4xbh]] - rNEP - rabbit<br />
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[[4zr5]] - rNEP + phosphoramidon<br />
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[[5v48]] - rNEP + thiorphan<br />
==References==
==References==

Current revision

Structure of glycosylated human neprilysin extracellular domain complex with phosphoramidon and Zn+2 ion (grey) (PDB entry 1dmt)

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

Michal Harel, Alexander Berchansky, Brenton Horne

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