5wyn - Revision history

OCA at 07:51, 22 November 2023

OCA — Wed, 22 Nov 2023 07:51:41 GMT

←Older revision		Revision as of 07:51, 22 November 2023
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	==HtrA2 Pathogenic Mutant==		==HtrA2 Pathogenic Mutant==
-	<StructureSection load='5wyn' size='340' side='right' caption='[[5wyn]], [[Resolution\|resolution]] 2.05Å' scene=''>	+	<StructureSection load='5wyn' size='340' side='right'caption='[[5wyn]], [[Resolution\|resolution]] 2.05Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5wyn]] is a 1 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Human Human~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5WYN OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5WYN FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5wyn]] 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=5WYN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5WYN 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=MES:~~2~~-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>~~</td></tr>	+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 2.05Å</td></tr>
-	<tr id='~~gene~~'><td class="sblockLbl"><b>[[~~Gene~~\|~~Gene~~:]]</b></td><td class="sblockDat"~~>HTRA2, OMI, PRSS25 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&~~id=~~9606 HUMAN])</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=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene></td></tr>
-	~~<tr id~~='~~activity'><td class~~=~~"sblockLbl"><b>Activity~~:~~</b~~></td><~~td class~~=~~"sblockDat"><span class~~=~~'plainlinks~~'>~~[http://en.wikipedia.org/wiki/HtrA2_peptidase HtrA2 peptidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.108 3.4.21.108]~~ </~~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=5wyn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5wyn OCA], [https://pdbe.org/5wyn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5wyn RCSB], [https://www.ebi.ac.uk/pdbsum/5wyn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5wyn 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=5wyn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5wyn OCA], [~~http~~://pdbe.org/5wyn PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5wyn RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5wyn PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5wyn ProSAT]</span></td></tr>	+
	</table>		</table>
	== Disease ==		== Disease ==
-	[~~[http~~://www.uniprot.org/uniprot/HTRA2_HUMAN HTRA2_HUMAN]] Defects in HTRA2 are the cause of Parkinson disease type 13 (PARK13) [MIM:[~~http~~://omim.org/entry/610297 610297]]. A complex neurodegenerative disorder characterized by bradykinesia, resting tremor, muscular rigidity and postural instability, as well as by a clinically significant response to treatment with levodopa. The pathology involves the loss of dopaminergic neurons in the substantia nigra and the presence of Lewy bodies (intraneuronal accumulations of aggregated proteins), in surviving neurons in various areas of the brain.<ref>PMID:15961413</ref> <ref>PMID:18401856</ref>	+	[https://www.uniprot.org/uniprot/HTRA2_HUMAN HTRA2_HUMAN] Defects in HTRA2 are the cause of Parkinson disease type 13 (PARK13) [MIM:[https://omim.org/entry/610297 610297]. A complex neurodegenerative disorder characterized by bradykinesia, resting tremor, muscular rigidity and postural instability, as well as by a clinically significant response to treatment with levodopa. The pathology involves the loss of dopaminergic neurons in the substantia nigra and the presence of Lewy bodies (intraneuronal accumulations of aggregated proteins), in surviving neurons in various areas of the brain.<ref>PMID:15961413</ref> <ref>PMID:18401856</ref>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/HTRA2_HUMAN HTRA2_HUMAN]] Serine protease that shows proteolytic activity against a non-specific substrate beta-casein. Promotes or induces cell death either by direct binding to and inhibition of BIRC proteins (also called inhibitor of apoptosis proteins, IAPs), leading to an increase in caspase activity, or by a BIRC inhibition-independent, caspase-independent and serine protease activity-dependent mechanism. Cleaves THAP5 and promotes its degradation during apoptosis. Isoform 2 seems to be proteolytically inactive.<ref>PMID:15200957</ref> <ref>PMID:19502560</ref>	+	[https://www.uniprot.org/uniprot/HTRA2_HUMAN HTRA2_HUMAN] Serine protease that shows proteolytic activity against a non-specific substrate beta-casein. Promotes or induces cell death either by direct binding to and inhibition of BIRC proteins (also called inhibitor of apoptosis proteins, IAPs), leading to an increase in caspase activity, or by a BIRC inhibition-independent, caspase-independent and serine protease activity-dependent mechanism. Cleaves THAP5 and promotes its degradation during apoptosis. Isoform 2 seems to be proteolytically inactive.<ref>PMID:15200957</ref> <ref>PMID:19502560</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 24:		Line 23:

	==See Also==		==See Also==
-	*[[Proteinase\|Proteinase]]	+	*[[Proteinase 3D structures\|Proteinase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~HtrA2 peptidase~~]]	+	[[Category: Homo sapiens]]
-	[[Category: ~~Human~~]]	+	[[Category: Large Structures]]
-	[[Category: Bose, K]]	+	[[Category: Bose K]]
-	[[Category: Wagh~~, A R]]~~	+	[[Category: Wagh AR]]
-	~~[[Category: Hydrolase]]~~	+
-	~~[[Category: Neurodegeneration]]~~	+
-	~~[[Category: Pathogenic mutant~~]]	+

OCA at 06:35, 24 October 2018

OCA — Wed, 24 Oct 2018 06:35:44 GMT

←Older revision		Revision as of 06:35, 24 October 2018
Line 22:		Line 22:
	</div>		</div>
	<div class="pdbe-citations 5wyn" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5wyn" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Proteinase\|Proteinase]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 07:51, 29 August 2018

OCA — Wed, 29 Aug 2018 07:51:52 GMT

←Older revision		Revision as of 07:51, 29 August 2018
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	<StructureSection load='5wyn' size='340' side='right' caption='[[5wyn]], [[Resolution\|resolution]] 2.05Å' scene=''>		<StructureSection load='5wyn' size='340' side='right' caption='[[5wyn]], [[Resolution\|resolution]] 2.05Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5wyn]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5WYN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5WYN FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5wyn]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5WYN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5WYN 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=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</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=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">HTRA2, OMI, PRSS25 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/HtrA2_peptidase HtrA2 peptidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.108 3.4.21.108] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/HtrA2_peptidase HtrA2 peptidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.108 3.4.21.108] </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=5wyn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5wyn OCA], [http://pdbe.org/5wyn PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5wyn RCSB], [http://www.ebi.ac.uk/pdbsum/5wyn PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5wyn 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=5wyn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5wyn OCA], [http://pdbe.org/5wyn PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5wyn RCSB], [http://www.ebi.ac.uk/pdbsum/5wyn PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5wyn ProSAT]</span></td></tr>
Line 12:		Line 13:
	== Function ==		== Function ==
	[[http://www.uniprot.org/uniprot/HTRA2_HUMAN HTRA2_HUMAN]] Serine protease that shows proteolytic activity against a non-specific substrate beta-casein. Promotes or induces cell death either by direct binding to and inhibition of BIRC proteins (also called inhibitor of apoptosis proteins, IAPs), leading to an increase in caspase activity, or by a BIRC inhibition-independent, caspase-independent and serine protease activity-dependent mechanism. Cleaves THAP5 and promotes its degradation during apoptosis. Isoform 2 seems to be proteolytically inactive.<ref>PMID:15200957</ref> <ref>PMID:19502560</ref>		[[http://www.uniprot.org/uniprot/HTRA2_HUMAN HTRA2_HUMAN]] Serine protease that shows proteolytic activity against a non-specific substrate beta-casein. Promotes or induces cell death either by direct binding to and inhibition of BIRC proteins (also called inhibitor of apoptosis proteins, IAPs), leading to an increase in caspase activity, or by a BIRC inhibition-independent, caspase-independent and serine protease activity-dependent mechanism. Cleaves THAP5 and promotes its degradation during apoptosis. Isoform 2 seems to be proteolytically inactive.<ref>PMID:15200957</ref> <ref>PMID:19502560</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Serine protease HtrA2 (High temperature requirement protease A2), is involved in apoptosis and protein quality control. However, one of its murine inactive mutants, (S276C aka mnd2) is associated with motor neuron degeneration 2. Similarly, this conserved mutation in human HtrA2 (hHtrA2) also renders the protease inactive, implicating pathogenicity. However, the structural determinants for its inactivation have not yet been elucidated. Here, using multidisciplinary approach, we studied the structural basis of inactivity associated with this mutation in hHtrA2. Characterization of secondary and tertiary structural properties, protein stability, oligomeric properties and enzyme activity for both wild type and mutant has been performed using biophysical and functional enzymology studies. The structural comparison at atomic resolution has been carried out using X-ray crystallography. While enzyme kinetics showed inactivity, spectroscopic probes did not identify any significant secondary structural changes in the mutant. X-ray crystallographic analysis of the mutant protein at 2A resolution highlighted the significance of a water molecule that plays important role in mediating intermolecular interactions for maintaining the functional ensemble of the protease. Overall, the crystallographic data, along with biophysical and enzymology studies helped decipher the structural basis of inactivity of hHtrA2S276C, which might pave way toward further investigating its correlation with aberration of normal cellular functions, hence pathogenicity.
		+
		+	Structural Basis of Inactivation of Human Counterpart of Mouse Motor Neuron Degeneration 2 Mutant in Serine Protease HtrA2.,Wagh AR, Bose K Biosci Rep. 2018 Aug 1. pii: BSR20181072. doi: 10.1042/BSR20181072. PMID:30068699<ref>PMID:30068699</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 5wyn" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>
Line 17:		Line 27:
	</StructureSection>		</StructureSection>
	[[Category: HtrA2 peptidase]]		[[Category: HtrA2 peptidase]]
		+	[[Category: Human]]
	[[Category: Bose, K]]		[[Category: Bose, K]]
	[[Category: Wagh, A R]]		[[Category: Wagh, A R]]

OCA at 21:40, 9 August 2018

OCA — Thu, 09 Aug 2018 21:40:53 GMT

←Older revision		Revision as of 21:40, 9 August 2018
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 5wyn ~~is ON HOLD until Aug~~ 05 ~~2019~~	+	==HtrA2 Pathogenic Mutant==
-		+	<StructureSection load='5wyn' size='340' side='right' caption='[[5wyn]], [[Resolution\|resolution]] 2.05Å' scene=''>
-	~~Authors~~: ~~Wagh~~, A.R., ~~Bose~~, K.	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[5wyn]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5WYN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5WYN FirstGlance]. <br>
-	~~Description~~: ~~HtrA2 Pathogenic Mutant~~	+	</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=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene></td></tr>
-	[[Category: ~~Unreleased Structures~~]]	+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/HtrA2_peptidase HtrA2 peptidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.108 3.4.21.108] </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=5wyn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5wyn OCA], [http://pdbe.org/5wyn PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5wyn RCSB], [http://www.ebi.ac.uk/pdbsum/5wyn PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5wyn ProSAT]</span></td></tr>
		+	</table>
		+	== Disease ==
		+	[[http://www.uniprot.org/uniprot/HTRA2_HUMAN HTRA2_HUMAN]] Defects in HTRA2 are the cause of Parkinson disease type 13 (PARK13) [MIM:[http://omim.org/entry/610297 610297]]. A complex neurodegenerative disorder characterized by bradykinesia, resting tremor, muscular rigidity and postural instability, as well as by a clinically significant response to treatment with levodopa. The pathology involves the loss of dopaminergic neurons in the substantia nigra and the presence of Lewy bodies (intraneuronal accumulations of aggregated proteins), in surviving neurons in various areas of the brain.<ref>PMID:15961413</ref> <ref>PMID:18401856</ref>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/HTRA2_HUMAN HTRA2_HUMAN]] Serine protease that shows proteolytic activity against a non-specific substrate beta-casein. Promotes or induces cell death either by direct binding to and inhibition of BIRC proteins (also called inhibitor of apoptosis proteins, IAPs), leading to an increase in caspase activity, or by a BIRC inhibition-independent, caspase-independent and serine protease activity-dependent mechanism. Cleaves THAP5 and promotes its degradation during apoptosis. Isoform 2 seems to be proteolytically inactive.<ref>PMID:15200957</ref> <ref>PMID:19502560</ref>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: HtrA2 peptidase]]
	[[Category: Bose, K]]		[[Category: Bose, K]]
-	[[Category: Wagh, A.R]]	+	[[Category: Wagh, A R]]
		+	[[Category: Hydrolase]]
		+	[[Category: Neurodegeneration]]
		+	[[Category: Pathogenic mutant]]

OCA at 16:49, 1 August 2018

OCA — Wed, 01 Aug 2018 16:49:02 GMT

←Older revision		Revision as of 16:49, 1 August 2018
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 5wyn is ON HOLD until ~~Jul 29~~ 2019	+	The entry 5wyn is ON HOLD until Aug 05 2019

	Authors: Wagh, A.R., Bose, K.		Authors: Wagh, A.R., Bose, K.

OCA at 05:38, 25 July 2018

OCA — Wed, 25 Jul 2018 05:38:40 GMT

←Older revision		Revision as of 05:38, 25 July 2018
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 5wyn is ON HOLD until Jul 22 2019	+	The entry 5wyn is ON HOLD until Jul 29 2019

	Authors: Wagh, A.R., Bose, K.		Authors: Wagh, A.R., Bose, K.

OCA at 05:03, 18 July 2018

OCA — Wed, 18 Jul 2018 05:03:06 GMT

←Older revision		Revision as of 05:03, 18 July 2018
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 5wyn is ON HOLD until Jul 15 2019	+	The entry 5wyn is ON HOLD until Jul 22 2019

	Authors: Wagh, A.R., Bose, K.		Authors: Wagh, A.R., Bose, K.

OCA at 03:51, 11 July 2018

OCA — Wed, 11 Jul 2018 03:51:31 GMT

←Older revision		Revision as of 03:51, 11 July 2018
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 5wyn is ON HOLD until Jul 08 2019	+	The entry 5wyn is ON HOLD until Jul 15 2019

	Authors: Wagh, A.R., Bose, K.		Authors: Wagh, A.R., Bose, K.

OCA at 05:27, 4 July 2018

OCA — Wed, 04 Jul 2018 05:27:48 GMT

←Older revision		Revision as of 05:27, 4 July 2018
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 5wyn is ON HOLD until Jul 01 2019	+	The entry 5wyn is ON HOLD until Jul 08 2019

	Authors: Wagh, A.R., Bose, K.		Authors: Wagh, A.R., Bose, K.

OCA at 03:45, 27 June 2018

OCA — Wed, 27 Jun 2018 03:45:59 GMT

←Older revision		Revision as of 03:45, 27 June 2018
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 5wyn is ON HOLD until ~~Jun 24~~ 2019	+	The entry 5wyn is ON HOLD until Jul 01 2019

	Authors: Wagh, A.R., Bose, K.		Authors: Wagh, A.R., Bose, K.