Neprilysin - Revision history

Michal Harel at 09:51, 21 January 2024

Michal Harel — Sun, 21 Jan 2024 09:51:36 GMT

←Older revision		Revision as of 09:51, 21 January 2024
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	== Relevance ==		== 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 like [[Sacubitril]] are tested as analgesics and anti-hypertensive agents.	+	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 ==

Michal Harel at 09:50, 21 January 2024

Michal Harel — Sun, 21 Jan 2024 09:50:16 GMT

←Older revision		Revision as of 09:50, 21 January 2024
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	== Relevance ==		== 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.	+	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]] are tested as analgesics and anti-hypertensive agents.

	== Structural highlights ==		== Structural highlights ==

Michal Harel at 09:28, 17 November 2021

Michal Harel — Wed, 17 Nov 2021 09:28:08 GMT

←Older revision		Revision as of 09:28, 17 November 2021
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	[[6gid]] - hNEP extracellular domain 52-750 - human<br />		[[6gid]] - hNEP extracellular domain 52-750 - human<br />
		+	[[6sh1]] - hNEP extracellular domain (mutant)<br />
		+	[[6sh2]] - hNEP extracellular domain (mutant) + natriuretic peptide<br />
	[[1dmt]] – hNEP extracellular domain + Zn + phosphoramidon <br />		[[1dmt]] – hNEP extracellular domain + Zn + phosphoramidon <br />
	[[4cth]] - hNEP extracellular domain (mutant) + Zn + phosphoramidon<br />		[[4cth]] - hNEP extracellular domain (mutant) + Zn + phosphoramidon<br />

Michal Harel at 08:03, 10 September 2020

Michal Harel — Thu, 10 Sep 2020 08:03:52 GMT

←Older revision		Revision as of 08:03, 10 September 2020
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	Updated on {{REVISIONDAY2}}-{{MONTHNAME\|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}		Updated on {{REVISIONDAY2}}-{{MONTHNAME\|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}

-	[[6gid]] - hNEP extracellular domain - human<br />	+	[[6gid]] - hNEP extracellular domain 52-750 - human<br />
	[[1dmt]] – hNEP extracellular domain + Zn + phosphoramidon <br />		[[1dmt]] – hNEP extracellular domain + Zn + phosphoramidon <br />
	[[4cth]] - hNEP extracellular domain (mutant) + Zn + phosphoramidon<br />		[[4cth]] - hNEP extracellular domain (mutant) + Zn + phosphoramidon<br />
	[[5jmy]] - hNEP extracellular domain + subitril<br />		[[5jmy]] - hNEP extracellular domain + subitril<br />
-	[[1r1h]], [[1r1i]], [[1r1j]], [[1y8j]], [[2qpj]], [[2yb9]] - hNEP extracellular domain + Zn + inhibitor<br />	+	[[1r1h]], [[1r1i]], [[1r1j]], [[1y8j]], [[2qpj]], [[2yb9]], [[6suk]], [[6svy]], [[6thp]], [[6xvp]] - hNEP extracellular domain + Zn + inhibitor<br />
	[[2yvc]] – NEP cytoplasmic tail + radixin - mouse<br />		[[2yvc]] – NEP cytoplasmic tail + radixin - mouse<br />
	[[4xbh]] - rNEP - rabbit<br />		[[4xbh]] - rNEP - rabbit<br />

Alexander Berchansky at 13:00, 22 July 2019

Alexander Berchansky — Mon, 22 Jul 2019 13:00:23 GMT

←Older revision		Revision as of 13:00, 22 July 2019
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	== Structural highlights ==		== Structural highlights ==
-	A <scene name='51/516479/Cv/2'>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/5'>Active site</scene>. Water molecules shown as red spheres.	+	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==

Michal Harel at 10:16, 12 August 2018

Michal Harel — Sun, 12 Aug 2018 10:16:32 GMT

←Older revision		Revision as of 10:16, 12 August 2018
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	Updated on {{REVISIONDAY2}}-{{MONTHNAME\|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}		Updated on {{REVISIONDAY2}}-{{MONTHNAME\|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}

-	[[1dmt]] – hNEP extracellular domain + Zn + phosphoramidon ~~– human~~<br />	+	[[6gid]] - hNEP extracellular domain - human<br />
		+	[[1dmt]] – hNEP extracellular domain + Zn + phosphoramidon <br />
	[[4cth]] - hNEP extracellular domain (mutant) + Zn + phosphoramidon<br />		[[4cth]] - hNEP extracellular domain (mutant) + Zn + phosphoramidon<br />
	[[5jmy]] - hNEP extracellular domain + subitril<br />		[[5jmy]] - hNEP extracellular domain + subitril<br />
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	[[4xbh]] - rNEP - rabbit<br />		[[4xbh]] - rNEP - rabbit<br />
	[[4zr5]] - rNEP + phosphoramidon<br />		[[4zr5]] - rNEP + phosphoramidon<br />
		+	[[5v48]] - rNEP + thiorphan<br />

	==References==		==References==

Michal Harel at 07:58, 21 August 2017

Michal Harel — Mon, 21 Aug 2017 07:58:48 GMT

←Older revision		Revision as of 07:58, 21 August 2017
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	[[1dmt]] – hNEP extracellular domain + Zn + phosphoramidon – human<br />		[[1dmt]] – hNEP extracellular domain + Zn + phosphoramidon – human<br />
	[[4cth]] - hNEP extracellular domain (mutant) + Zn + phosphoramidon<br />		[[4cth]] - hNEP extracellular domain (mutant) + Zn + phosphoramidon<br />
		+	[[5jmy]] - hNEP extracellular domain + subitril<br />
	[[1r1h]], [[1r1i]], [[1r1j]], [[1y8j]], [[2qpj]], [[2yb9]] - hNEP extracellular domain + Zn + 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<br />
		+	[[4xbh]] - rNEP - rabbit<br />
		+	[[4zr5]] - rNEP + phosphoramidon<br />

	==References==		==References==

Alexander Berchansky at 07:29, 1 June 2016

Alexander Berchansky — Wed, 01 Jun 2016 07:29:47 GMT

←Older revision		Revision as of 07:29, 1 June 2016
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	== Structural highlights ==		== Structural highlights ==
-	A tetrahedrally coordinated Zn atom interacts with the NEP inhibitor and is involved in the catalysis<ref>PMID: 10669592</ref>.	+	A <scene name='51/516479/Cv/2'>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/5'>Active site</scene>. Water molecules shown as red spheres.

	==3D structures of neprilysin==		==3D structures of neprilysin==

Alexander Berchansky at 06:51, 1 June 2016

Alexander Berchansky — Wed, 01 Jun 2016 06:51:45 GMT

←Older revision		Revision as of 06:51, 1 June 2016
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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=''>	+	<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.

Michal Harel at 06:59, 8 May 2016

Michal Harel — Sun, 08 May 2016 06:59:25 GMT

←Older revision		Revision as of 06:59, 8 May 2016
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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 and Zn+2 ion (grey) (PDB entry [[1dmt]])' scene=''>
	== 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.
Line 7:		Line 7:

	== Structural highlights ==		== Structural highlights ==
-	A tetrahedrally coordinated Zn atom interacts with the NEP inhibitor and is involved in the catalysis<ref>PMID: ~~1669592~~</ref>.	+	A tetrahedrally coordinated Zn atom interacts with the NEP inhibitor and is involved in the catalysis<ref>PMID: 10669592</ref>.

	==3D structures of neprilysin==		==3D structures of neprilysin==