Neprilysin
From Proteopedia
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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=''> | <StructureSection load='1dmt' size='400' side='right' caption='Structure of glycosylated human neprilysin extracellular domain complex with phosphoramidon (PDB entry [[1dmt]])' scene=''> | ||
| + | == 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. | ||
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| + | == Relevance == | ||
| + | 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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| + | == Structural highlights == | ||
| + | A tetrahedrally coordinated Zn atom interacts with the NEP inhibitor and is involved in the catalysis<ref>PMID: 1669592</ref>. | ||
| - | '''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> Its signalling has also been implicated in cardiovascular disease.<ref>PMID: 21046489</ref> NEP turns off peptide signalling events at the cell surface. NEP is found in brain tissue and is an integral membrane protein. | ||
==3D structures of neprilysin== | ==3D structures of neprilysin== | ||
Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}} | Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}} | ||
| - | [[1dmt]] – hNEP extracellular domain + phosphoramidon – human<br /> | + | [[1dmt]] – hNEP extracellular domain + Zn + phosphoramidon – human<br /> |
| - | [[4cth]] - hNEP extracellular domain (mutant) + phosphoramidon<br /> | + | [[4cth]] - hNEP extracellular domain (mutant) + Zn + phosphoramidon<br /> |
| - | [[1r1h]], [[1r1i]], [[1r1j]], [[1y8j]], [[2qpj]], [[2yb9]] - hNEP extracellular domain + inhibitor<br /> | + | [[1r1h]], [[1r1i]], [[1r1j]], [[1y8j]], [[2qpj]], [[2yb9]] - hNEP extracellular domain + Zn + inhibitor<br /> |
[[2yvc]] – NEP cytoplasmic tail + radixin - mouse | [[2yvc]] – NEP cytoplasmic tail + radixin - mouse | ||
Revision as of 06:57, 8 May 2016
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