2zeq - Revision history

OCA at 13:57, 13 March 2024

OCA — Wed, 13 Mar 2024 13:57:13 GMT

←Older revision		Revision as of 13:57, 13 March 2024
Line 3:		Line 3:
	<StructureSection load='2zeq' size='340' side='right'caption='[[2zeq]], [[Resolution\|resolution]] 1.65Å' scene=''>		<StructureSection load='2zeq' size='340' side='right'caption='[[2zeq]], [[Resolution\|resolution]] 1.65Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[2zeq]] is a 1 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Lk3_transgenic_mice Lk3 transgenic mice~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2ZEQ OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=2ZEQ FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[2zeq]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2ZEQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2ZEQ FirstGlance]. <br>
-	</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=2zeq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2zeq OCA], [~~http~~://pdbe.org/2zeq PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=2zeq RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/2zeq PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=2zeq ProSAT]</span></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]] 1.65Å</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=2zeq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2zeq OCA], [https://pdbe.org/2zeq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2zeq RCSB], [https://www.ebi.ac.uk/pdbsum/2zeq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2zeq ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/~~PRKN2_MOUSE PRKN2_MOUSE]~~] Functions within a multiprotein E3 ubiquitin ligase complex, catalyzing the covalent attachment of ubiquitin moieties onto substrate proteins, ~~such as BCL2,~~ SYT11, CCNE1, GPR37, STUB1, ~~a 22 kDa O-linked glycosylated isoform of~~ SNCAIP, ~~SEPT5~~, ZNF746 and AIMP2. Mediates monoubiquitination as well as 'Lys-48'-linked and 'Lys-63'-linked polyubiquitination of substrates depending on the context. Participates in the removal and/or detoxification of abnormally folded or damaged protein by mediating 'Lys-63'-linked polyubiquitination of misfolded proteins such as PARK7: 'Lys-63'-linked polyubiquitinated misfolded proteins are then recognized by HDAC6, leading to their recruitment to aggresomes, followed by degradation. Mediates 'Lys-63'-linked polyubiquitination of SNCAIP, possibly playing a role in Lewy-body formation. Mediates monoubiquitination of BCL2, thereby acting as a positive regulator of autophagy. ~~Promotes~~ the autophagic degradation of dysfunctional depolarized mitochondria. ~~Mediates~~ 'Lys-48'-linked ~~polyubiquitination of ZNF746~~, ~~followed~~ by degradation of ~~ZNF746~~ by the ~~proteasome~~; ~~possibly playing a role~~ in ~~role~~ in ~~regulation~~ of ~~neuron death~~. Limits the production of reactive oxygen species (ROS). ~~Loss~~ of ~~this~~ ubiquitin ligase activity ~~appears to be~~ the ~~mechanism underlying pathogenesis~~ of ~~PARK2~~. May protect neurons against alpha synuclein toxicity, proteasomal dysfunction, GPR37 accumulation, and kainate-induced excitotoxicity. May play a role in controlling neurotransmitter trafficking at the presynaptic terminal and in calcium-dependent exocytosis~~. Regulates cyclin-E during neuronal apoptosis~~. May represent a tumor suppressor gene (By similarity).<ref>PMID:~~15105460~~</ref>	+	[https://www.uniprot.org/uniprot/PRKN_MOUSE PRKN_MOUSE] Functions within a multiprotein E3 ubiquitin ligase complex, catalyzing the covalent attachment of ubiquitin moieties onto substrate proteins (PubMed:32047033, PubMed:29311685). Substrates include SYT11 and VDAC1 (PubMed:32047033, PubMed:29311685). Other substrates are BCL2, CCNE1, GPR37, RHOT1/MIRO1, MFN1, MFN2, STUB1, SNCAIP, SEPTIN5, TOMM20, USP30, ZNF746, MIRO1 and AIMP2 (By similarity). Mediates monoubiquitination as well as 'Lys-6', 'Lys-11', 'Lys-48'-linked and 'Lys-63'-linked polyubiquitination of substrates depending on the context (PubMed:32047033, PubMed:25474007). Participates in the removal and/or detoxification of abnormally folded or damaged protein by mediating 'Lys-63'-linked polyubiquitination of misfolded proteins such as PARK7: 'Lys-63'-linked polyubiquitinated misfolded proteins are then recognized by HDAC6, leading to their recruitment to aggresomes, followed by degradation (By similarity). Mediates 'Lys-63'-linked polyubiquitination of a 22 kDa O-linked glycosylated isoform of SNCAIP, possibly playing a role in Lewy-body formation (By similarity). Mediates monoubiquitination of BCL2, thereby acting as a positive regulator of autophagy (By similarity). Protects against mitochondrial dysfunction during cellular stress, by acting downstream of PINK1 to coordinate mitochondrial quality control mechanisms that remove and replace dysfunctional mitochondrial components (PubMed:32047033, PubMed:25474007, PubMed:22082830, PubMed:24898855). Depending on the severity of mitochondrial damage and/or dysfunction, activity ranges from preventing apoptosis and stimulating mitochondrial biogenesis to regulating mitochondrial dynamics and eliminating severely damaged mitochondria via mitophagy (PubMed:32047033, PubMed:22082830, PubMed:24898855). Activation and recruitment onto the outer membrane of damaged/dysfunctional mitochondria (OMM) requires PINK1-mediated phosphorylation of both PRKN and ubiquitin (PubMed:25474007). After mitochondrial damage, functions with PINK1 to mediate the decision between mitophagy or preventing apoptosis by inducing either the poly- or monoubiquitination of VDAC1, respectively; polyubiquitination of VDAC1 promotes mitophagy, while monoubiquitination of VDAC1 decreases mitochondrial calcium influx which ultimately inhibits apoptosis (PubMed:32047033). When cellular stress results in irreversible mitochondrial damage, promotes the autophagic degradation of dysfunctional depolarized mitochondria (mitophagy) by promoting the ubiquitination of mitochondrial proteins such as TOMM20, RHOT1/MIRO1, MFN1 and USP30 (PubMed:21753002). Preferentially assembles 'Lys-6'-, 'Lys-11'- and 'Lys-63'-linked polyubiquitin chains, leading to mitophagy (By similarity). The PINK1-PRKN pathway also promotes fission of damaged mitochondria by PINK1-mediated phosphorylation which promotes the PRKN-dependent degradation of mitochondrial proteins involved in fission such as MFN2 (PubMed:24192653). This prevents the refusion of unhealthy mitochondria with the mitochondrial network or initiates mitochondrial fragmentation facilitating their later engulfment by autophagosomes (By similarity). Regulates motility of damaged mitochondria via the ubiquitination and subsequent degradation of MIRO1 and MIRO2; in motor neurons, this likely inhibits mitochondrial intracellular anterograde transport along the axons which probably increases the chance of the mitochondria undergoing mitophagy in the soma (By similarity). Involved in mitochondrial biogenesis via the 'Lys-48'-linked polyubiquitination of transcriptional repressor ZNF746/PARIS which leads to its subsequent proteasomal degradation and allows activation of the transcription factor PPARGC1A (By similarity). Limits the production of reactive oxygen species (ROS) (By similarity). Regulates cyclin-E during neuronal apoptosis (By similarity). In collaboration with CHPF isoform 2, may enhance cell viability and protect cells from oxidative stress (PubMed:22082830). Independently of its ubiquitin ligase activity, protects from apoptosis by the transcriptional repression of p53/TP53 (PubMed:19801972). May protect neurons against alpha synuclein toxicity, proteasomal dysfunction, GPR37 accumulation, and kainate-induced excitotoxicity (By similarity). May play a role in controlling neurotransmitter trafficking at the presynaptic terminal and in calcium-dependent exocytosis. May represent a tumor suppressor gene (By similarity).[UniProtKB:O60260]<ref>PMID:19801972</ref> <ref>PMID:21753002</ref> <ref>PMID:22082830</ref> <ref>PMID:24192653</ref> <ref>PMID:24898855</ref> <ref>PMID:25474007</ref> <ref>PMID:29311685</ref> <ref>PMID:32047033</ref>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
Line 18:		Line 19:
	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2zeq ConSurf].		</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2zeq ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
-	<div style="background-color:#fffaf0;">
-	== Publication Abstract from PubMed ==
-	Parkin is the gene product identified as the major cause of autosomal recessive juvenile Parkinsonism (AR-JP). Parkin, a ubiquitin ligase E3, contains a unique ubiquitin-like domain in its N-terminus designated Uld which is assumed to be a interaction domain with the Rpn 10 subunit of 26S proteasome. To elucidate the structural and functional role of Uld in parkin at the atomic level, the X-ray crystal structure of murine Uld was determined and a molecular dynamics simulation of wild Uld and its five mutants (K27N, R33Q, R42P, K48A and V56E) identified from AR-JP patients was performed. Murine Uld consists of two alpha helices [Ile23-Arg33 (alpha1) and Val56-Gln57 (alpha2)] and five beta strands [Met1-Phe7 (beta1), Tyr11-Asp18 (beta2), Leu41-Phe45 (beta3), Lys48-Pro51 (beta4) and Ser65-Arg72 (beta5)] and its overall structure is essentially the same as that of human ubiquitin with a 1.22 A rmsd for the backbone atoms of residues 1-76; however, the sequential identity and similarity between both molecules are 32% and 63%, respectively. This close resemblance is due to the core structure built by same hydrogen bond formations between and within the backbone chains of alpha1 and beta1/2/5 secondary structure elements and by nearly the same hydrophobic interactions formed between the nonpolar amino acids of their secondary structures. The side chain NetaH of Lys27 on the alpha1 helix was crucial to the stabilization of the spatial orientations of beta3 and beta4 strands, possible binding region with Rpn 10 subunit, through three hydrogen bonds. The MD simulations showed the K27N and R33Q mutations increase the structural fluctuation of these beta strands including the alpha1 helix. Reversely, the V56E mutant restricted the spatial flexibility at the periphery of the short alpha2 helix by the interactions between the polar atoms of Glu56 and Ser19 residues. However, a large fluctuation of beta4 strand with respect to beta5 strand was induced in the R42P mutant, because of the impossibility of forming paired hydrogen bonds of Pro for Arg42 in wild Uld. The X-ray structure showed that the side chains of Asp39, Gln40 and Arg42 at the N-terminal periphery of beta3 strand protrude from the molecular surface of Uld and participate in hydrogen bonds with the polar residues of neighboring Ulds. Thus, the MD simulation suggests that the mutation substitution of Pro for Arg42 not only causes the large fluctuation of beta3 strand in the Uld but also leads to the loss of the ability of Uld to trap the Rpn 10 subunit. In contrast, the MD simulation of K48A mutant showed little influence on the beta3-beta4 loop structure, but a large fluctuation of Lys48 side chain, suggesting the importance of flexibility of this side chain for the interaction with the Rpn 10 subunit. The present results would be important in elucidating the impaired proteasomal binding mechanism of parkin in AR-JP.
-
-	Crystal structure and molecular dynamics simulation of ubiquitin-like domain of murine parkin.,Tomoo K, Mukai Y, In Y, Miyagawa H, Kitamura K, Yamano A, Shindo H, Ishida T Biochim Biophys Acta. 2008 Jul-Aug;1784(7-8):1059-67. Epub 2008 Apr 25. PMID:18485927<ref>PMID:18485927</ref>
-
-	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	</div>
-	<div class="pdbe-citations 2zeq" style="background-color:#fffaf0;"></div>
-
-	==See Also==
-	*[[Ubiquitin protein ligase 3D structures\|Ubiquitin protein ligase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
Line 35:		Line 24:
	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: ~~Lk3 transgenic mice~~]]	+	[[Category: Mus musculus]]
-	[[Category: Tomoo, K]]	+	[[Category: Tomoo K]]
-	~~[[Category: Alternative splicing]]~~	+
-	~~[[Category: Cell junction]]~~	+
-	~~[[Category: Cell projection]]~~	+
-	~~[[Category: Cytoplasm]]~~	+
-	~~[[Category: Endoplasmic reticulum]]~~	+
-	~~[[Category: Ligase]]~~	+
-	~~[[Category: Membrane]]~~	+
-	~~[[Category: Metal-binding]]~~	+
-	~~[[Category: Nucleus]]~~	+
-	~~[[Category: Parkin]]~~	+
-	~~[[Category: Postsynaptic cell membrane]]~~	+
-	~~[[Category: S-nitrosylation]]~~	+
-	~~[[Category: Synapse]]~~	+
-	~~[[Category: Ubiquitin-like domain]]~~	+
-	~~[[Category: Ubl conjugation]]~~	+
-	~~[[Category: Ubl conjugation pathway]]~~	+
-	~~[[Category: Zinc]]~~	+
-	~~[[Category: Zinc-finger~~]]	+

OCA at 12:03, 29 July 2020

OCA — Wed, 29 Jul 2020 12:03:26 GMT

←Older revision		Revision as of 12:03, 29 July 2020
Line 1:		Line 1:

	==Crystal structure of ubiquitin-like domain of murine Parkin==		==Crystal structure of ubiquitin-like domain of murine Parkin==
-	<StructureSection load='2zeq' size='340' side='right' caption='[[2zeq]], [[Resolution\|resolution]] 1.65Å' scene=''>	+	<StructureSection load='2zeq' size='340' side='right'caption='[[2zeq]], [[Resolution\|resolution]] 1.65Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[2zeq]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2ZEQ OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=2ZEQ FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[2zeq]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2ZEQ OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=2ZEQ FirstGlance]. <br>
-	</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=2zeq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2zeq OCA], [http://pdbe.org/2zeq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2zeq RCSB], [http://www.ebi.ac.uk/pdbsum/2zeq PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2zeq ProSAT]</span></td></tr>	+	</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=2zeq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2zeq OCA], [http://pdbe.org/2zeq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2zeq RCSB], [http://www.ebi.ac.uk/pdbsum/2zeq PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2zeq ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 29:		Line 29:

	==See Also==		==See Also==
-	*[[Ubiquitin protein ligase\|Ubiquitin protein ligase]]	+	*[[Ubiquitin protein ligase 3D structures\|Ubiquitin protein ligase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Large Structures]]
	[[Category: Lk3 transgenic mice]]		[[Category: Lk3 transgenic mice]]
	[[Category: Tomoo, K]]		[[Category: Tomoo, K]]

OCA at 07:10, 18 October 2018

OCA — Thu, 18 Oct 2018 07:10:24 GMT

←Older revision		Revision as of 07:10, 18 October 2018
Line 1:		Line 1:
		+
	==Crystal structure of ubiquitin-like domain of murine Parkin==		==Crystal structure of ubiquitin-like domain of murine Parkin==
	<StructureSection load='2zeq' size='340' side='right' caption='[[2zeq]], [[Resolution\|resolution]] 1.65Å' scene=''>		<StructureSection load='2zeq' size='340' side='right' caption='[[2zeq]], [[Resolution\|resolution]] 1.65Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[2zeq]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2ZEQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2ZEQ FirstGlance]. <br>		<table><tr><td colspan='2'>[[2zeq]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2ZEQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2ZEQ FirstGlance]. <br>
-	</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=2zeq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2zeq OCA], [http://pdbe.org/2zeq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2zeq RCSB], [http://www.ebi.ac.uk/pdbsum/2zeq PDBsum]</span></td></tr>	+	</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=2zeq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2zeq OCA], [http://pdbe.org/2zeq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2zeq RCSB], [http://www.ebi.ac.uk/pdbsum/2zeq PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2zeq ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 11:		Line 12:
	Check<jmol>		Check<jmol>
	<jmolCheckbox>		<jmolCheckbox>
-	<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ze/2zeq_consurf.spt"</scriptWhenChecked>	+	<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ze/2zeq_consurf.spt"</scriptWhenChecked>
	<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>		<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
	<text>to colour the structure by Evolutionary Conservation</text>		<text>to colour the structure by Evolutionary Conservation</text>
Line 35:		Line 36:
	[[Category: Lk3 transgenic mice]]		[[Category: Lk3 transgenic mice]]
	[[Category: Tomoo, K]]		[[Category: Tomoo, K]]
		+	[[Category: Alternative splicing]]
	[[Category: Cell junction]]		[[Category: Cell junction]]
	[[Category: Cell projection]]		[[Category: Cell projection]]
		+	[[Category: Cytoplasm]]
	[[Category: Endoplasmic reticulum]]		[[Category: Endoplasmic reticulum]]
	[[Category: Ligase]]		[[Category: Ligase]]
Line 47:		Line 50:
	[[Category: Synapse]]		[[Category: Synapse]]
	[[Category: Ubiquitin-like domain]]		[[Category: Ubiquitin-like domain]]
		+	[[Category: Ubl conjugation]]
	[[Category: Ubl conjugation pathway]]		[[Category: Ubl conjugation pathway]]
		+	[[Category: Zinc]]
	[[Category: Zinc-finger]]		[[Category: Zinc-finger]]

OCA at 16:52, 7 February 2016

OCA — Sun, 07 Feb 2016 16:52:07 GMT

←Older revision		Revision as of 16:52, 7 February 2016
Line 2:		Line 2:
	<StructureSection load='2zeq' size='340' side='right' caption='[[2zeq]], [[Resolution\|resolution]] 1.65Å' scene=''>		<StructureSection load='2zeq' size='340' side='right' caption='[[2zeq]], [[Resolution\|resolution]] 1.65Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[2zeq]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/~~Mus_musculus Mus musculus~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2ZEQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2ZEQ FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[2zeq]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2ZEQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2ZEQ FirstGlance]. <br>
-	</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=2zeq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2zeq OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2zeq RCSB], [http://www.ebi.ac.uk/pdbsum/2zeq PDBsum]</span></td></tr>	+	</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=2zeq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2zeq OCA], [http://pdbe.org/2zeq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2zeq RCSB], [http://www.ebi.ac.uk/pdbsum/2zeq PDBsum]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 15:		Line 15:
	<text>to colour the structure by Evolutionary Conservation</text>		<text>to colour the structure by Evolutionary Conservation</text>
	</jmolCheckbox>		</jmolCheckbox>
-	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/~~chain_selection~~.php?pdb_ID=~~2ata~~ ConSurf].	+	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2zeq ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
Line 25:		Line 25:
	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	</div>		</div>
		+	<div class="pdbe-citations 2zeq" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 32:		Line 33:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Mus musculus~~]]	+	[[Category: Lk3 transgenic mice]]
	[[Category: Tomoo, K]]		[[Category: Tomoo, K]]
	[[Category: Cell junction]]		[[Category: Cell junction]]

OCA at 16:49, 24 December 2014

OCA — Wed, 24 Dec 2014 16:49:43 GMT

←Older revision		Revision as of 16:49, 24 December 2014
Line 3:		Line 3:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[2zeq]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2ZEQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2ZEQ FirstGlance]. <br>		<table><tr><td colspan='2'>[[2zeq]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2ZEQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2ZEQ FirstGlance]. <br>
-	</td></tr><tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2zeq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2zeq OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2zeq RCSB], [http://www.ebi.ac.uk/pdbsum/2zeq PDBsum]</span></td></tr>	+	</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=2zeq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2zeq OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2zeq RCSB], [http://www.ebi.ac.uk/pdbsum/2zeq PDBsum]</span></td></tr>
-	<table>	+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/PRKN2_MOUSE PRKN2_MOUSE]] Functions within a multiprotein E3 ubiquitin ligase complex, catalyzing the covalent attachment of ubiquitin moieties onto substrate proteins, such as BCL2, SYT11, CCNE1, GPR37, STUB1, a 22 kDa O-linked glycosylated isoform of SNCAIP, SEPT5, ZNF746 and AIMP2. Mediates monoubiquitination as well as 'Lys-48'-linked and 'Lys-63'-linked polyubiquitination of substrates depending on the context. Participates in the removal and/or detoxification of abnormally folded or damaged protein by mediating 'Lys-63'-linked polyubiquitination of misfolded proteins such as PARK7: 'Lys-63'-linked polyubiquitinated misfolded proteins are then recognized by HDAC6, leading to their recruitment to aggresomes, followed by degradation. Mediates 'Lys-63'-linked polyubiquitination of SNCAIP, possibly playing a role in Lewy-body formation. Mediates monoubiquitination of BCL2, thereby acting as a positive regulator of autophagy. Promotes the autophagic degradation of dysfunctional depolarized mitochondria. Mediates 'Lys-48'-linked polyubiquitination of ZNF746, followed by degradation of ZNF746 by the proteasome; possibly playing a role in role in regulation of neuron death. Limits the production of reactive oxygen species (ROS). Loss of this ubiquitin ligase activity appears to be the mechanism underlying pathogenesis of PARK2. May protect neurons against alpha synuclein toxicity, proteasomal dysfunction, GPR37 accumulation, and kainate-induced excitotoxicity. May play a role in controlling neurotransmitter trafficking at the presynaptic terminal and in calcium-dependent exocytosis. Regulates cyclin-E during neuronal apoptosis. May represent a tumor suppressor gene (By similarity).<ref>PMID:15105460</ref>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
Line 31:		Line 33:
	</StructureSection>		</StructureSection>
	[[Category: Mus musculus]]		[[Category: Mus musculus]]
-	[[Category: Tomoo, K.]]	+	[[Category: Tomoo, K]]
	[[Category: Cell junction]]		[[Category: Cell junction]]
	[[Category: Cell projection]]		[[Category: Cell projection]]

OCA at 05:27, 2 October 2014

OCA — Thu, 02 Oct 2014 05:27:24 GMT

←Older revision		Revision as of 05:27, 2 October 2014
Line 1:		Line 1:
-	[[~~Image~~:2zeq.~~png\|left~~\|200px]]	+	==Crystal structure of ubiquitin-like domain of murine Parkin==
		+	<StructureSection load='2zeq' size='340' side='right' caption='[[2zeq]], [[Resolution\|resolution]] 1.65Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[2zeq]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2ZEQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2ZEQ FirstGlance]. <br>
		+	</td></tr><tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2zeq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2zeq OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2zeq RCSB], [http://www.ebi.ac.uk/pdbsum/2zeq PDBsum]</span></td></tr>
		+	<table>
		+	== Evolutionary Conservation ==
		+	[[Image:Consurf_key_small.gif\|200px\|right]]
		+	Check<jmol>
		+	<jmolCheckbox>
		+	<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ze/2zeq_consurf.spt"</scriptWhenChecked>
		+	<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
		+	<text>to colour the structure by Evolutionary Conservation</text>
		+	</jmolCheckbox>
		+	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].
		+	<div style="clear:both"></div>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Parkin is the gene product identified as the major cause of autosomal recessive juvenile Parkinsonism (AR-JP). Parkin, a ubiquitin ligase E3, contains a unique ubiquitin-like domain in its N-terminus designated Uld which is assumed to be a interaction domain with the Rpn 10 subunit of 26S proteasome. To elucidate the structural and functional role of Uld in parkin at the atomic level, the X-ray crystal structure of murine Uld was determined and a molecular dynamics simulation of wild Uld and its five mutants (K27N, R33Q, R42P, K48A and V56E) identified from AR-JP patients was performed. Murine Uld consists of two alpha helices [Ile23-Arg33 (alpha1) and Val56-Gln57 (alpha2)] and five beta strands [Met1-Phe7 (beta1), Tyr11-Asp18 (beta2), Leu41-Phe45 (beta3), Lys48-Pro51 (beta4) and Ser65-Arg72 (beta5)] and its overall structure is essentially the same as that of human ubiquitin with a 1.22 A rmsd for the backbone atoms of residues 1-76; however, the sequential identity and similarity between both molecules are 32% and 63%, respectively. This close resemblance is due to the core structure built by same hydrogen bond formations between and within the backbone chains of alpha1 and beta1/2/5 secondary structure elements and by nearly the same hydrophobic interactions formed between the nonpolar amino acids of their secondary structures. The side chain NetaH of Lys27 on the alpha1 helix was crucial to the stabilization of the spatial orientations of beta3 and beta4 strands, possible binding region with Rpn 10 subunit, through three hydrogen bonds. The MD simulations showed the K27N and R33Q mutations increase the structural fluctuation of these beta strands including the alpha1 helix. Reversely, the V56E mutant restricted the spatial flexibility at the periphery of the short alpha2 helix by the interactions between the polar atoms of Glu56 and Ser19 residues. However, a large fluctuation of beta4 strand with respect to beta5 strand was induced in the R42P mutant, because of the impossibility of forming paired hydrogen bonds of Pro for Arg42 in wild Uld. The X-ray structure showed that the side chains of Asp39, Gln40 and Arg42 at the N-terminal periphery of beta3 strand protrude from the molecular surface of Uld and participate in hydrogen bonds with the polar residues of neighboring Ulds. Thus, the MD simulation suggests that the mutation substitution of Pro for Arg42 not only causes the large fluctuation of beta3 strand in the Uld but also leads to the loss of the ability of Uld to trap the Rpn 10 subunit. In contrast, the MD simulation of K48A mutant showed little influence on the beta3-beta4 loop structure, but a large fluctuation of Lys48 side chain, suggesting the importance of flexibility of this side chain for the interaction with the Rpn 10 subunit. The present results would be important in elucidating the impaired proteasomal binding mechanism of parkin in AR-JP.

-	~~{{STRUCTURE_2zeq\| PDB=2zeq \| SCENE= }}~~	+	Crystal structure and molecular dynamics simulation of ubiquitin-like domain of murine parkin.,Tomoo K, Mukai Y, In Y, Miyagawa H, Kitamura K, Yamano A, Shindo H, Ishida T Biochim Biophys Acta. 2008 Jul-Aug;1784(7-8):1059-67. Epub 2008 Apr 25. PMID:18485927<ref>PMID:18485927</ref>

-	~~===Crystal structure~~ of ~~ubiquitin-like domain~~ of ~~murine Parkin===~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>

-	~~{{ABSTRACT_PUBMED_18485927}}~~	+	==See Also==
-		+	*[[Ubiquitin protein ligase\|Ubiquitin protein ligase]]
-	==~~About this Structure~~==	+	== References ==
-	[[~~2zeq~~]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2ZEQ OCA].	+	<references/>
-		+	__TOC__
-	==~~Reference~~==	+	</StructureSection>
-	<~~ref group="xtra">PMID:018485927<~~/~~ref~~><~~references group="xtra"~~/>	+
	[[Category: Mus musculus]]		[[Category: Mus musculus]]
	[[Category: Tomoo, K.]]		[[Category: Tomoo, K.]]

OCA: Protected "2zeq" [edit=sysop:move=sysop]

OCA — Mon, 07 Jan 2013 22:56:23 GMT

Protected "2zeq" [edit=sysop:move=sysop]

←Older revision

Revision as of 22:56, 7 January 2013

OCA at 22:56, 7 January 2013

OCA — Mon, 07 Jan 2013 22:56:20 GMT

←Older revision		Revision as of 22:56, 7 January 2013
Line 1:		Line 1:
-	{{Seed}}
	[[Image:2zeq.png\|left\|200px]]		[[Image:2zeq.png\|left\|200px]]

-	<!--
-	The line below this paragraph, containing "STRUCTURE_2zeq", creates the "Structure Box" on the page.
-	You may change the PDB parameter (which sets the PDB file loaded into the applet)
-	or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-	or leave the SCENE parameter empty for the default display.
-	-->
	{{STRUCTURE_2zeq\| PDB=2zeq \| SCENE= }}		{{STRUCTURE_2zeq\| PDB=2zeq \| SCENE= }}

	===Crystal structure of ubiquitin-like domain of murine Parkin===		===Crystal structure of ubiquitin-like domain of murine Parkin===

-
-	<!--
-	The line below this paragraph, {{ABSTRACT_PUBMED_18485927}}, adds the Publication Abstract to the page
-	(as it appears on PubMed at http://www.pubmed.gov), where 18485927 is the PubMed ID number.
-	-->
	{{ABSTRACT_PUBMED_18485927}}		{{ABSTRACT_PUBMED_18485927}}

	==About this Structure==		==About this Structure==
-	~~2ZEQ~~ is a 1 chain structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2ZEQ OCA].	+	[[2zeq]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2ZEQ OCA].

	==Reference==		==Reference==
-	<ref group="xtra">PMID:~~18485927~~</ref><references group="xtra"/>	+	<ref group="xtra">PMID:018485927</ref><references group="xtra"/>
	[[Category: Mus musculus]]		[[Category: Mus musculus]]
	[[Category: Tomoo, K.]]		[[Category: Tomoo, K.]]
-	[[Category: Alternative splicing]]
	[[Category: Cell junction]]		[[Category: Cell junction]]
	[[Category: Cell projection]]		[[Category: Cell projection]]
-	[[Category: Cytoplasm]]
	[[Category: Endoplasmic reticulum]]		[[Category: Endoplasmic reticulum]]
	[[Category: Ligase]]		[[Category: Ligase]]
Line 40:		Line 26:
	[[Category: Synapse]]		[[Category: Synapse]]
	[[Category: Ubiquitin-like domain]]		[[Category: Ubiquitin-like domain]]
-	[[Category: Ubl conjugation]]
	[[Category: Ubl conjugation pathway]]		[[Category: Ubl conjugation pathway]]
-	[[Category: Zinc]]
	[[Category: Zinc-finger]]		[[Category: Zinc-finger]]
-
-	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Feb 16 15:14:53 2009''

OCA at 13:14, 16 February 2009

OCA — Mon, 16 Feb 2009 13:14:56 GMT

←Older revision		Revision as of 13:14, 16 February 2009
Line 1:		Line 1:
	{{Seed}}		{{Seed}}
-	[[Image:2zeq.~~jpg~~\|left\|200px]]	+	[[Image:2zeq.png\|left\|200px]]

	<!--		<!--
Line 20:		Line 20:

	==About this Structure==		==About this Structure==
-	2ZEQ is a ~~[[Single protein]]~~ structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2ZEQ OCA].	+	2ZEQ is a 1 chain structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2ZEQ OCA].

	==Reference==		==Reference==
-	Crystal structure and molecular dynamics simulation of ubiquitin-like domain of murine parkin., Tomoo K, Mukai Y, In Y, Miyagawa H, Kitamura K, Yamano A, Shindo H, Ishida T, Biochim Biophys Acta. 2008 Jul-Aug;1784(7-8):1059-67. Epub 2008 Apr 25. PMID:~~[http:~~//~~www.ncbi.nlm.nih.gov/pubmed/18485927 18485927]~~	+	<ref group="xtra">PMID:18485927</ref><references group="xtra"/>
	[[Category: Mus musculus]]		[[Category: Mus musculus]]
-	[[Category: Single protein]]
	[[Category: Tomoo, K.]]		[[Category: Tomoo, K.]]
	[[Category: Alternative splicing]]		[[Category: Alternative splicing]]
Line 46:		Line 45:
	[[Category: Zinc-finger]]		[[Category: Zinc-finger]]

-	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on ~~Wed Aug 20 12~~:13:~~12 2008~~''	+	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Feb 16 15:14:53 2009''

OCA at 09:13, 20 August 2008

OCA — Wed, 20 Aug 2008 09:13:13 GMT

←Older revision		Revision as of 09:13, 20 August 2008
Line 1:		Line 1:
-	~~'''Unreleased structure'''~~	+	{{Seed}}
		+	[[Image:2zeq.jpg\|left\|200px]]

-	The ~~entry 2zeq~~ is ~~ON HOLD~~ ~~until Dec 14 2009~~	+	<!--
		+	The line below this paragraph, containing "STRUCTURE_2zeq", creates the "Structure Box" on the page.
		+	You may change the PDB parameter (which sets the PDB file loaded into the applet)
		+	or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
		+	or leave the SCENE parameter empty for the default display.
		+	-->
		+	{{STRUCTURE_2zeq\| PDB=2zeq \| SCENE= }}

-	~~Authors: Tomoo, K., Mukai, Y., In, Y., Yamano, A., Shindo, H., Ishida, T.~~	+	===Crystal structure of ubiquitin-like domain of murine Parkin===

-	Description: Crystal structure of ubiquitin-like domain of murine Parkin

		+	<!--
		+	The line below this paragraph, {{ABSTRACT_PUBMED_18485927}}, adds the Publication Abstract to the page
		+	(as it appears on PubMed at http://www.pubmed.gov), where 18485927 is the PubMed ID number.
		+	-->
		+	{{ABSTRACT_PUBMED_18485927}}

-	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed ~~Jun 11 09~~:07:51 2008''	+	==About this Structure==
		+	2ZEQ is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2ZEQ OCA].
		+
		+	==Reference==
		+	Crystal structure and molecular dynamics simulation of ubiquitin-like domain of murine parkin., Tomoo K, Mukai Y, In Y, Miyagawa H, Kitamura K, Yamano A, Shindo H, Ishida T, Biochim Biophys Acta. 2008 Jul-Aug;1784(7-8):1059-67. Epub 2008 Apr 25. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/18485927 18485927]
		+	[[Category: Mus musculus]]
		+	[[Category: Single protein]]
		+	[[Category: Tomoo, K.]]
		+	[[Category: Alternative splicing]]
		+	[[Category: Cell junction]]
		+	[[Category: Cell projection]]
		+	[[Category: Cytoplasm]]
		+	[[Category: Endoplasmic reticulum]]
		+	[[Category: Ligase]]
		+	[[Category: Membrane]]
		+	[[Category: Metal-binding]]
		+	[[Category: Nucleus]]
		+	[[Category: Parkin]]
		+	[[Category: Postsynaptic cell membrane]]
		+	[[Category: S-nitrosylation]]
		+	[[Category: Synapse]]
		+	[[Category: Ubiquitin-like domain]]
		+	[[Category: Ubl conjugation]]
		+	[[Category: Ubl conjugation pathway]]
		+	[[Category: Zinc]]
		+	[[Category: Zinc-finger]]
		+
		+	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Aug 20 12:13:12 2008''