5abw - Revision history

OCA at 04:50, 25 May 2023

OCA — Thu, 25 May 2023 04:50:17 GMT

←Older revision		Revision as of 04:50, 25 May 2023
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	<StructureSection load='5abw' size='340' side='right'caption='[[5abw]], [[Resolution\|resolution]] 1.60Å' scene=''>		<StructureSection load='5abw' size='340' side='right'caption='[[5abw]], [[Resolution\|resolution]] 1.60Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5abw]] is a 1 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5ABW OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5ABW FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5abw]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5ABW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5ABW FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=WQQ:1-(3-CHLOROPHENYL)-5-(3,5-DIMETHYLISOXAZOL-4-YL)-6-METHYL-N-[4-(METHYLSULFONYL)BENZYL]-2-OXO-1,2-DIHYDROPYRIDINE-3-CARBOXAMIDE'>WQQ</scene~~></td></tr>~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=WQQ:1-(3-CHLOROPHENYL)-5-(3,5-DIMETHYLISOXAZOL-4-YL)-6-METHYL-N-[4-(METHYLSULFONYL)BENZYL]-2-OXO-1,2-DIHYDROPYRIDINE-3-CARBOXAMIDE'>WQQ</scene></td></tr>
-	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Leukocyte_elastase Leukocyte elastase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.37 3.4.21.37] </span></td></tr>	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5abw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5abw OCA], [https://pdbe.org/5abw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5abw RCSB], [https://www.ebi.ac.uk/pdbsum/5abw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5abw ProSAT]</span></td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5abw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5abw OCA], [~~http~~://pdbe.org/5abw PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5abw RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5abw PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5abw ProSAT]</span></td></tr>	+
	</table>		</table>
	== Disease ==		== Disease ==
-	[~~[http~~://www.uniprot.org/uniprot/ELNE_HUMAN ELNE_HUMAN]] Defects in ELANE are a cause of cyclic haematopoiesis (CH) [MIM:[~~http~~://omim.org/entry/162800 162800]]; also known as cyclic neutropenia. CH is an autosomal dominant disease in which blood-cell production from the bone marrow oscillates with 21-day periodicity. Circulating neutrophils vary between almost normal numbers and zero. During intervals of neutropenia, affected individuals are at risk for opportunistic infection. Monocytes, platelets, lymphocytes and reticulocytes also cycle with the same frequency.<ref>PMID:14673143</ref> <ref>PMID:10581030</ref> Defects in ELANE are the cause of neutropenia severe congenital autosomal dominant type 1 (SCN1) [MIM:[~~http~~://omim.org/entry/202700 202700]]. SCN1 is a disorder of hematopoiesis characterized by a maturation arrest of granulopoiesis at the level of promyelocytes with peripheral blood absolute neutrophil counts below 0.5 x 10(9)/l and early onset of severe bacterial infections.<ref>PMID:20220065</ref>	+	[https://www.uniprot.org/uniprot/ELNE_HUMAN ELNE_HUMAN] Defects in ELANE are a cause of cyclic haematopoiesis (CH) [MIM:[https://omim.org/entry/162800 162800]; also known as cyclic neutropenia. CH is an autosomal dominant disease in which blood-cell production from the bone marrow oscillates with 21-day periodicity. Circulating neutrophils vary between almost normal numbers and zero. During intervals of neutropenia, affected individuals are at risk for opportunistic infection. Monocytes, platelets, lymphocytes and reticulocytes also cycle with the same frequency.<ref>PMID:14673143</ref> <ref>PMID:10581030</ref> Defects in ELANE are the cause of neutropenia severe congenital autosomal dominant type 1 (SCN1) [MIM:[https://omim.org/entry/202700 202700]. SCN1 is a disorder of hematopoiesis characterized by a maturation arrest of granulopoiesis at the level of promyelocytes with peripheral blood absolute neutrophil counts below 0.5 x 10(9)/l and early onset of severe bacterial infections.<ref>PMID:20220065</ref>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/ELNE_HUMAN ELNE_HUMAN]] Modifies the functions of natural killer cells, monocytes and granulocytes. Inhibits C5a-dependent neutrophil enzyme release and chemotaxis.<ref>PMID:15140022</ref>	+	[https://www.uniprot.org/uniprot/ELNE_HUMAN ELNE_HUMAN] Modifies the functions of natural killer cells, monocytes and granulocytes. Inhibits C5a-dependent neutrophil enzyme release and chemotaxis.<ref>PMID:15140022</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	~~[[Category: Leukocyte elastase]]~~	+	[[Category: Li VM]]
-	[[Category: Li~~, V M~~]]	+	[[Category: Schaefer M]]
-	[[Category: Schaefer, M]]	+	[[Category: Von Nussbaum F]]
-	[[Category: ~~VonNussbaum,~~ F]]	+
-	~~[[Category: Hydrolase]]~~	+
-	~~[[Category: Hydrolase-inhibitor complex]]~~	+
-	~~[[Category: Protease]]~~	+
-	~~[[Category: Trypsin family fold~~]]	+

OCA at 07:11, 3 July 2019

OCA — Wed, 03 Jul 2019 07:11:45 GMT

←Older revision		Revision as of 07:11, 3 July 2019
Line 1:		Line 1:

	==Neutrophil elastase inhibitors for the treatment of (cardio)pulmonary diseases==		==Neutrophil elastase inhibitors for the treatment of (cardio)pulmonary diseases==
-	<StructureSection load='5abw' size='340' side='right' caption='[[5abw]], [[Resolution\|resolution]] 1.60Å' scene=''>	+	<StructureSection load='5abw' size='340' side='right'caption='[[5abw]], [[Resolution\|resolution]] 1.60Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[5abw]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5ABW OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5ABW FirstGlance]. <br>		<table><tr><td colspan='2'>[[5abw]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5ABW OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5ABW FirstGlance]. <br>
Line 21:		Line 21:
	</div>		</div>
	<div class="pdbe-citations 5abw" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5abw" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Elastase 3D structures\|Elastase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
Line 26:		Line 29:
	</StructureSection>		</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
		+	[[Category: Large Structures]]
	[[Category: Leukocyte elastase]]		[[Category: Leukocyte elastase]]
	[[Category: Li, V M]]		[[Category: Li, V M]]

OCA at 09:43, 22 March 2017

OCA — Wed, 22 Mar 2017 09:43:17 GMT

←Older revision		Revision as of 09:43, 22 March 2017
Line 1:		Line 1:
		+
	==Neutrophil elastase inhibitors for the treatment of (cardio)pulmonary diseases==		==Neutrophil elastase inhibitors for the treatment of (cardio)pulmonary diseases==
	<StructureSection load='5abw' size='340' side='right' caption='[[5abw]], [[Resolution\|resolution]] 1.60Å' scene=''>		<StructureSection load='5abw' size='340' side='right' caption='[[5abw]], [[Resolution\|resolution]] 1.60Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[5abw]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5ABW OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5ABW FirstGlance]. <br>		<table><tr><td colspan='2'>[[5abw]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5ABW OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5ABW FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=WQQ:1-(3-CHLOROPHENYL)-5-(3,5-DIMETHYLISOXAZOL-4-YL)-6-METHYL-N-[4-(METHYLSULFONYL)BENZYL]-2-OXO-1,2-DIHYDROPYRIDINE-3-CARBOXAMIDE'>WQQ~~</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG~~</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=WQQ:1-(3-CHLOROPHENYL)-5-(3,5-DIMETHYLISOXAZOL-4-YL)-6-METHYL-N-[4-(METHYLSULFONYL)BENZYL]-2-OXO-1,2-DIHYDROPYRIDINE-3-CARBOXAMIDE'>WQQ</scene></td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Leukocyte_elastase Leukocyte elastase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.37 3.4.21.37] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Leukocyte_elastase Leukocyte elastase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.37 3.4.21.37] </span></td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5abw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5abw OCA], [http://www.rcsb.org/pdb/explore.do?structureId=5abw RCSB], [http://www.ebi.ac.uk/pdbsum/5abw PDBsum]</span></td></tr>	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5abw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5abw OCA], [http://pdbe.org/5abw PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5abw RCSB], [http://www.ebi.ac.uk/pdbsum/5abw PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5abw ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 11:		Line 12:
	== Function ==		== Function ==
	[[http://www.uniprot.org/uniprot/ELNE_HUMAN ELNE_HUMAN]] Modifies the functions of natural killer cells, monocytes and granulocytes. Inhibits C5a-dependent neutrophil enzyme release and chemotaxis.<ref>PMID:15140022</ref>		[[http://www.uniprot.org/uniprot/ELNE_HUMAN ELNE_HUMAN]] Modifies the functions of natural killer cells, monocytes and granulocytes. Inhibits C5a-dependent neutrophil enzyme release and chemotaxis.<ref>PMID:15140022</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Alpha-1 antitrypsin deficiency is linked with an increased risk of suffering from lung emphysema. This discovery from the 1960s led to the development of the protease-antiprotease (im)balance hypothesis: Overshooting protease concentrations, especially high levels of elastase were deemed to have an destructive effect on lung tissue. Consequently, it was postulated that efficient elastase inhibitors could alleviate the situation in patients. However, despite intensive drug discovery efforts, even five decades later, no neutrophil elastase inhibitors are available for a disease-modifying treatment of (cardio)pulmonary diseases such as chronic obstructive pulmonary disease. Here, we critically review the attempts to develop effective human neutrophil elastase inhibitors while strongly focussing on recent developments. On purpose and with perspective distortion we focus on recent developments. One aim of this review is to classify the known HNE inhibitors into several generations, according to their binding modes. In general, there seem to be three major challenges in the development of suitable elastase inhibitors: (1) assuring sufficient potency, (2) securing selectivity, and (3) achieving metabolic stability especially under pathophysiological conditions. Impressive achievements have been made since 2001 with the identification of potent nonreactive, reversible small molecule inhibitors. The most modern inhibitors bind HNE via an induced fit with a frozen bioactive conformation that leads to a significant boost in potency, selectivity, and stability ('pre-adaptive pharmacophores'). These 5th generation inhibitors might succeed in re-establishing the protease-antiprotease balance in patients for the first time.
		+
		+	Neutrophil elastase inhibitors for the treatment of (cardio)pulmonary diseases: Into clinical testing with pre-adaptive pharmacophores.,von Nussbaum F, Li VM Bioorg Med Chem Lett. 2015 Oct 15;25(20):4370-81. doi:, 10.1016/j.bmcl.2015.08.049. Epub 2015 Aug 20. PMID:26358162<ref>PMID:26358162</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 5abw" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>

OCA: Protected "5abw" [edit=sysop:move=sysop]

OCA — Thu, 20 Aug 2015 12:27:48 GMT

Protected "5abw" [edit=sysop:move=sysop]

←Older revision

Revision as of 12:27, 20 August 2015

OCA: New page: ==Neutrophil elastase inhibitors for the treatment of (cardio)pulmonary diseases== == Structural highlights ==
<table><tr><td colspan='2'>[[5abw]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5ABW OCA]. For a guided tour on the structure components use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5ABW FirstGlance]. 
</td></tr><tr id='ligand'><td class="sblockLbl">[[Ligand|Ligands:]]</td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=WQQ:1-(3-CHLOROPHENYL)-5-(3,5-DIMETHYLISOXAZOL-4-YL)-6-METHYL-N-[4-(METHYLSULFONYL)BENZYL]-2-OXO-1,2-DIHYDROPYRIDINE-3-CARBOXAMIDE'>WQQ</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
<tr id='activity'><td class="sblockLbl">Activity:</td><td class="sblockDat">[http://en.wikipedia.org/wiki/Leukocyte_elastase Leukocyte elastase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.37 3.4.21.37] </td></tr>
<tr id='resources'><td class="sblockLbl">Resources:</td><td class="sblockDat">[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5abw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5abw OCA], [http://www.rcsb.org/pdb/explore.do?structureId=5abw RCSB], [http://www.ebi.ac.uk/pdbsum/5abw PDBsum]</td></tr>
</table>
== Disease ==
[[http://www.uniprot.org/uniprot/ELNE_HUMAN ELNE_HUMAN]] Defects in ELANE are a cause of cyclic haematopoiesis (CH) [MIM:[http://omim.org/entry/162800 162800]]; also known as cyclic neutropenia. CH is an autosomal dominant disease in which blood-cell production from the bone marrow oscillates with 21-day periodicity. Circulating neutrophils vary between almost normal numbers and zero. During intervals of neutropenia, affected individuals are at risk for opportunistic infection. Monocytes, platelets, lymphocytes and reticulocytes also cycle with the same frequency.<ref>PMID:14673143</ref> <ref>PMID:10581030</ref> Defects in ELANE are the cause of neutropenia severe congenital autosomal dominant type 1 (SCN1) [MIM:[http://omim.org/entry/202700 202700]]. SCN1 is a disorder of hematopoiesis characterized by a maturation arrest of granulopoiesis at the level of promyelocytes with peripheral blood absolute neutrophil counts below 0.5 x 10(9)/l and early onset of severe bacterial infections.<ref>PMID:20220065</ref>
== Function ==
[[http://www.uniprot.org/uniprot/ELNE_HUMAN ELNE_HUMAN]] Modifies the functions of natural killer cells, monocytes and granulocytes. Inhibits C5a-dependent neutrophil enzyme release and chemotaxis.<ref>PMID:15140022</ref>
== References ==
<references/>
TOC
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Leukocyte elastase]]
[[Category: Li, V M]]
[[Category: Schaefer, M]]
[[Category: VonNussbaum, F]]
[[Category: Hydrolase]]
[[Category: Hydrolase-inhibitor complex]]
[[Category: Protease]]
[[Category: Trypsin family fold]]