5tnz - Revision history

OCA at 15:42, 6 March 2024

OCA — Wed, 06 Mar 2024 15:42:15 GMT

←Older revision		Revision as of 15:42, 6 March 2024
Line 3:		Line 3:
	<StructureSection load='5tnz' size='340' side='right'caption='[[5tnz]], [[Resolution\|resolution]] 1.75Å' scene=''>		<StructureSection load='5tnz' size='340' side='right'caption='[[5tnz]], [[Resolution\|resolution]] 1.75Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5tnz]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5TNZ OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=5TNZ FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5tnz]] 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=5TNZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5TNZ FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat" id="~~ligandDat~~">~~<scene name='pdbligand=MES:2~~-~~(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>~~, ~~<scene name='pdbligand=NA:SODIUM+ION'>NA</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]] 1.75Å</td></tr>
-	<tr id='~~related~~'><td class="sblockLbl"><b>[[~~Related_structure~~\|~~Related~~:]]</b></td><td class="sblockDat"~~>[[5m3n\|5m3n]], [[5m3o\|5m3o]], [[5to0\|5to0]], [[5tny\|5tny]], [[5to1\|5to1]]</td></tr>~~	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</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=5tnz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5tnz OCA], [https://pdbe.org/5tnz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5tnz RCSB], [https://www.ebi.ac.uk/pdbsum/5tnz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5tnz ProSAT]</span></td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://proteopedia.org/fgij/fg.htm?mol=5tnz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5tnz OCA], [~~http~~://pdbe.org/5tnz PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5tnz RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5tnz PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5tnz 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;">~~	+
-	~~== Publication Abstract from PubMed ==~~	+
-	HtrA2 (high-temperature requirement 2) is a human mitochondrial protease that has a role in apoptosis and Parkinson's disease. The structure of HtrA2 with an intact catalytic triad was determined, revealing a conformational change in the active site loops, involving mainly the regulatory LD loop, which resulted in burial of the catalytic serine relative to the previously reported structure of the proteolytically inactive mutant. Mutations in the loops surrounding the active site that significantly restricted their mobility, reduced proteolytic activity both in vitro and in cells, suggesting that regulation of HtrA2 activity cannot be explained by a simple transition to an activated conformational state with enhanced active site accessibility. Manipulation of solvent viscosity highlighted an unusual bi-phasic behavior of the enzymatic activity, which together with MD calculations supports the importance of motion in the regulation of the activity of HtrA2. HtrA2 is an unusually thermostable enzyme (TM=97.3 degrees C), a trait often associated with structural rigidity, not dynamic motion. We suggest that this thermostability functions to provide a stable scaffold for the observed loop motions, allowing them a relatively free conformational search within a rather restricted volume.	+
-		+
-	Molecular motion regulates the activity of the Mitochondrial Serine Protease HtrA2.,Merski M, Moreira C, Abreu RM, Ramos MJ, Fernandes PA, Martins LM, Pereira PJB, Macedo-Ribeiro S Cell Death Dis. 2017 Oct 12;8(10):e3119. doi: 10.1038/cddis.2017.487. PMID:29022916<ref>PMID:29022916</ref>	+
-		+
-	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~	+
-	~~</div>~~	+
-	~~<div class="pdbe-citations 5tnz" style="background-color:#fffaf0;"></div~~>	+

	==See Also==		==See Also==
-	*[[Proteinase\|Proteinase]]
	*[[Proteinase 3D structures\|Proteinase 3D structures]]		*[[Proteinase 3D structures\|Proteinase 3D structures]]
	== References ==		== References ==
Line 30:		Line 19:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~HtrA2 peptidase~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Macedo-Ribeiro, S]]	+	[[Category: Macedo-Ribeiro S]]
-	[[Category: Merski, M]]	+	[[Category: Merski M]]
-	[[Category: Pereira~~, P J.B]]~~	+	[[Category: Pereira PJB]]
-	~~[[Category: Hydrolase]]~~	+
-	~~[[Category: Mitochondrial protease]]~~	+
-	~~[[Category: Serine protease]]~~	+
-	~~[[Category: Trimeric dynamic~~]]	+

OCA at 12:14, 23 September 2020

OCA — Wed, 23 Sep 2020 12:14:33 GMT

←Older revision		Revision as of 12:14, 23 September 2020
Line 1:		Line 1:

	==HtrA2 S142D mutant==		==HtrA2 S142D mutant==
-	<StructureSection load='5tnz' size='340' side='right' caption='[[5tnz]], [[Resolution\|resolution]] 1.75Å' scene=''>	+	<StructureSection load='5tnz' size='340' side='right'caption='[[5tnz]], [[Resolution\|resolution]] 1.75Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5tnz]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5TNZ OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5TNZ FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5tnz]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5TNZ OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5TNZ FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5m3n\|5m3n]], [[5m3o\|5m3o]], [[5to0\|5to0]], [[5tny\|5tny]], [[5to1\|5to1]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5m3n\|5m3n]], [[5m3o\|5m3o]], [[5to0\|5to0]], [[5tny\|5tny]], [[5to1\|5to1]]</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=5tnz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5tnz OCA], [http://pdbe.org/5tnz PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5tnz RCSB], [http://www.ebi.ac.uk/pdbsum/5tnz PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5tnz ProSAT]</span></td></tr>	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5tnz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5tnz OCA], [http://pdbe.org/5tnz PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5tnz RCSB], [http://www.ebi.ac.uk/pdbsum/5tnz PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5tnz ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 22:		Line 22:
	</div>		</div>
	<div class="pdbe-citations 5tnz" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5tnz" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Proteinase\|Proteinase]]
		+	*[[Proteinase 3D structures\|Proteinase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
Line 27:		Line 31:
	</StructureSection>		</StructureSection>
	[[Category: HtrA2 peptidase]]		[[Category: HtrA2 peptidase]]
		+	[[Category: Large Structures]]
	[[Category: Macedo-Ribeiro, S]]		[[Category: Macedo-Ribeiro, S]]
	[[Category: Merski, M]]		[[Category: Merski, M]]

OCA at 07:02, 25 October 2017

OCA — Wed, 25 Oct 2017 07:02:59 GMT

←Older revision		Revision as of 07:02, 25 October 2017
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 5tnz is ~~ON HOLD~~ ~~until Paper~~ Publication	+	==HtrA2 S142D mutant==
		+	<StructureSection load='5tnz' size='340' side='right' caption='[[5tnz]], [[Resolution\|resolution]] 1.75Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[5tnz]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5TNZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5TNZ FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5m3n\|5m3n]], [[5m3o\|5m3o]], [[5to0\|5to0]], [[5tny\|5tny]], [[5to1\|5to1]]</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=5tnz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5tnz OCA], [http://pdbe.org/5tnz PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5tnz RCSB], [http://www.ebi.ac.uk/pdbsum/5tnz PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5tnz 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>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	HtrA2 (high-temperature requirement 2) is a human mitochondrial protease that has a role in apoptosis and Parkinson's disease. The structure of HtrA2 with an intact catalytic triad was determined, revealing a conformational change in the active site loops, involving mainly the regulatory LD loop, which resulted in burial of the catalytic serine relative to the previously reported structure of the proteolytically inactive mutant. Mutations in the loops surrounding the active site that significantly restricted their mobility, reduced proteolytic activity both in vitro and in cells, suggesting that regulation of HtrA2 activity cannot be explained by a simple transition to an activated conformational state with enhanced active site accessibility. Manipulation of solvent viscosity highlighted an unusual bi-phasic behavior of the enzymatic activity, which together with MD calculations supports the importance of motion in the regulation of the activity of HtrA2. HtrA2 is an unusually thermostable enzyme (TM=97.3 degrees C), a trait often associated with structural rigidity, not dynamic motion. We suggest that this thermostability functions to provide a stable scaffold for the observed loop motions, allowing them a relatively free conformational search within a rather restricted volume.

-	~~Authors~~:	+	Molecular motion regulates the activity of the Mitochondrial Serine Protease HtrA2.,Merski M, Moreira C, Abreu RM, Ramos MJ, Fernandes PA, Martins LM, Pereira PJB, Macedo-Ribeiro S Cell Death Dis. 2017 Oct 12;8(10):e3119. doi: 10.1038/cddis.2017.487. PMID:29022916<ref>PMID:29022916</ref>

-	~~Description~~:	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased Structures~~]]	+	</div>
		+	<div class="pdbe-citations 5tnz" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: HtrA2 peptidase]]
		+	[[Category: Macedo-Ribeiro, S]]
		+	[[Category: Merski, M]]
		+	[[Category: Pereira, P J.B]]
		+	[[Category: Hydrolase]]
		+	[[Category: Mitochondrial protease]]
		+	[[Category: Serine protease]]
		+	[[Category: Trimeric dynamic]]

OCA at 16:56, 2 November 2016

OCA — Wed, 02 Nov 2016 16:56:57 GMT

←Older revision		Revision as of 16:56, 2 November 2016
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 5tnz is ON HOLD	+	The entry 5tnz is ON HOLD until Paper Publication

	Authors:		Authors:

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

OCA — Wed, 26 Oct 2016 17:17:10 GMT

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

←Older revision

Revision as of 17:17, 26 October 2016

OCA: New page: '''Unreleased structure''' The entry 5tnz is ON HOLD Authors: Description: Category: Unreleased Structures

OCA — Wed, 26 Oct 2016 17:17:08 GMT

New page: '''Unreleased structure''' The entry 5tnz is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 5tnz is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]