2myl - Revision history

OCA at 08:35, 15 November 2023

OCA — Wed, 15 Nov 2023 08:35:42 GMT

←Older revision		Revision as of 08:35, 15 November 2023
Line 1:		Line 1:

	==Cullin3 - BTB interface: a novel target for stapled peptides==		==Cullin3 - BTB interface: a novel target for stapled peptides==
-	<StructureSection load='2myl' size='340' side='right'caption='[[2myl~~]], [[NMR_Ensembles_of_Models \| 20 NMR models~~]]' scene=''>	+	<StructureSection load='2myl' size='340' side='right'caption='[[2myl]]' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[2myl]] is a 1 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2MYL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2MYL FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[2myl]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2MYL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2MYL FirstGlance]. <br>
-	</td></tr><tr id='~~NonStdRes~~'><td class="sblockLbl"><b>[[~~Non-Standard_Residue~~\|~~NonStd Res~~:]]</b></td><td class="sblockDat"~~><scene name~~=~~'pdbligand=MK8:2-METHYL-L-NORLEUCINE'>MK8</scene~~></td></tr>	+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr>
-	<tr id='~~related~~'><td class="sblockLbl"><b>[[~~Related_structure~~\|~~Related~~:]]</b></td><td class="sblockDat"><~~div style~~='~~overflow~~: ~~auto; max~~-~~height: 3em;~~'>~~[[2mym\|2mym]]~~</~~div~~></td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MK8:2-METHYL-L-NORLEUCINE'>MK8</scene></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=2myl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2myl OCA], [https://pdbe.org/2myl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2myl RCSB], [https://www.ebi.ac.uk/pdbsum/2myl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2myl ProSAT]</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=2myl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2myl OCA], [https://pdbe.org/2myl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2myl RCSB], [https://www.ebi.ac.uk/pdbsum/2myl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2myl ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
-	[[https://www.uniprot.org/uniprot/CUL3_HUMAN CUL3_HUMAN]] Pseudohypoaldosteronism type 2E. Defects in CUL3 are the cause of Pseudohypoaldosteronism type 2E (PHA2E) [MIM:[https://omim.org/entry/614496 614496]]. An autosomal dominant disorder characterized by severe hypertension, hyperkalemia, hyperchloremia, hyperchloremic metabolic acidosis, and correction of physiologic abnormalities by thiazide diuretics.<ref>PMID:22266938</ref>	+	[https://www.uniprot.org/uniprot/CUL3_HUMAN CUL3_HUMAN] Pseudohypoaldosteronism type 2E. Defects in CUL3 are the cause of Pseudohypoaldosteronism type 2E (PHA2E) [MIM:[https://omim.org/entry/614496 614496]. An autosomal dominant disorder characterized by severe hypertension, hyperkalemia, hyperchloremia, hyperchloremic metabolic acidosis, and correction of physiologic abnormalities by thiazide diuretics.<ref>PMID:22266938</ref>
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/CUL3_HUMAN CUL3_HUMAN]] Core component of multiple cullin-RING-based BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complexes which mediate the ubiquitination and subsequent proteasomal degradation of target proteins. As a scaffold protein may contribute to catalysis through positioning of the substrate and the ubiquitin-conjugating enzyme. The E3 ubiquitin-protein ligase activity of the complex is dependent on the neddylation of the cullin subunit and is inhibited by the association of the deneddylated cullin subunit with TIP120A/CAND1 (By similarity). The functional specificity of the BCR complex depends on the BTB domain-containing protein as the susbstrate recognition component. BCR(SPOP) is involved in ubiquitination of BMI1/PCGF4, H2AFY and DAXX, and probably GLI2 or GLI3. BCR(KLHL9-KLHL13) controls the dynamic behavior of AURKB on mitotic chromosomes and thereby coordinates faithful mitotic progression and completion of cytokinesis. BCR(KLHL12) is involved in ER-Golgi transport by regulating the size of COPII coats, thereby playing a key role in collagen export, which is required for embryonic stem (ES) cells division: BCR(KLHL12) acts by mediating monoubiquitination of SEC31 (SEC31A or SEC31B). BCR(KLHL3) acts as a regulator of ion transport in the distal nephron; possibly by mediating ubiquitination of SLC12A3/NCC. Involved in ubiquitination of cyclin E and of cyclin D1 (in vitro) thus involved in regulation of G1/S transition.<ref>PMID:10500095</ref> <ref>PMID:11311237</ref> <ref>PMID:15897469</ref> <ref>PMID:16524876</ref> <ref>PMID:17543862</ref> <ref>PMID:22358839</ref>	+	[https://www.uniprot.org/uniprot/CUL3_HUMAN CUL3_HUMAN] Core component of multiple cullin-RING-based BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complexes which mediate the ubiquitination and subsequent proteasomal degradation of target proteins. As a scaffold protein may contribute to catalysis through positioning of the substrate and the ubiquitin-conjugating enzyme. The E3 ubiquitin-protein ligase activity of the complex is dependent on the neddylation of the cullin subunit and is inhibited by the association of the deneddylated cullin subunit with TIP120A/CAND1 (By similarity). The functional specificity of the BCR complex depends on the BTB domain-containing protein as the susbstrate recognition component. BCR(SPOP) is involved in ubiquitination of BMI1/PCGF4, H2AFY and DAXX, and probably GLI2 or GLI3. BCR(KLHL9-KLHL13) controls the dynamic behavior of AURKB on mitotic chromosomes and thereby coordinates faithful mitotic progression and completion of cytokinesis. BCR(KLHL12) is involved in ER-Golgi transport by regulating the size of COPII coats, thereby playing a key role in collagen export, which is required for embryonic stem (ES) cells division: BCR(KLHL12) acts by mediating monoubiquitination of SEC31 (SEC31A or SEC31B). BCR(KLHL3) acts as a regulator of ion transport in the distal nephron; possibly by mediating ubiquitination of SLC12A3/NCC. Involved in ubiquitination of cyclin E and of cyclin D1 (in vitro) thus involved in regulation of G1/S transition.<ref>PMID:10500095</ref> <ref>PMID:11311237</ref> <ref>PMID:15897469</ref> <ref>PMID:16524876</ref> <ref>PMID:17543862</ref> <ref>PMID:22358839</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 28:		Line 28:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Malgieri, G]]	+	[[Category: Malgieri G]]
-	[[Category: Palmieri, M]]	+	[[Category: Palmieri M]]
-	[[Category: Russo, L]]	+	[[Category: Russo L]]
-	~~[[Category: Protein]]~~	+
-	~~[[Category: Protein binding~~]]	+

OCA at 09:03, 23 February 2022

OCA — Wed, 23 Feb 2022 09:03:57 GMT

OCA at 06:29, 20 May 2020

OCA — Wed, 20 May 2020 06:29:25 GMT

←Older revision		Revision as of 06:29, 20 May 2020
Line 1:		Line 1:

	==Cullin3 - BTB interface: a novel target for stapled peptides==		==Cullin3 - BTB interface: a novel target for stapled peptides==
-	<StructureSection load='2myl' size='340' side='right' caption='[[2myl]], [[NMR_Ensembles_of_Models \| 20 NMR models]]' scene=''>	+	<StructureSection load='2myl' size='340' side='right'caption='[[2myl]], [[NMR_Ensembles_of_Models \| 20 NMR models]]' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[2myl]] is a 1 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2MYL OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=2MYL FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[2myl]] is a 1 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2MYL OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=2MYL FirstGlance]. <br>
	</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MK8:2-METHYL-L-NORLEUCINE'>MK8</scene></td></tr>		</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MK8:2-METHYL-L-NORLEUCINE'>MK8</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2mym\|2mym]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2mym\|2mym]]</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=2myl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2myl OCA], [http://pdbe.org/2myl PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2myl RCSB], [http://www.ebi.ac.uk/pdbsum/2myl PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2myl 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=2myl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2myl OCA], [http://pdbe.org/2myl PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2myl RCSB], [http://www.ebi.ac.uk/pdbsum/2myl PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2myl ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 23:		Line 23:

	==See Also==		==See Also==
-	*[[Cullin\|Cullin]]	+	*[[Cullin 3D structures\|Cullin 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Large Structures]]
	[[Category: Malgieri, G]]		[[Category: Malgieri, G]]
	[[Category: Palmieri, M]]		[[Category: Palmieri, M]]

OCA at 16:56, 15 August 2018

OCA — Wed, 15 Aug 2018 16:56:16 GMT

←Older revision		Revision as of 16:56, 15 August 2018
Line 6:		Line 6:
	</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MK8:2-METHYL-L-NORLEUCINE'>MK8</scene></td></tr>		</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MK8:2-METHYL-L-NORLEUCINE'>MK8</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2mym\|2mym]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2mym\|2mym]]</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=2myl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2myl OCA], [http://pdbe.org/2myl PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2myl RCSB], [http://www.ebi.ac.uk/pdbsum/2myl 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=2myl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2myl OCA], [http://pdbe.org/2myl PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2myl RCSB], [http://www.ebi.ac.uk/pdbsum/2myl PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2myl ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==

OCA at 07:40, 1 June 2016

OCA — Wed, 01 Jun 2016 07:40:32 GMT

←Older revision		Revision as of 07:40, 1 June 2016
Line 1:		Line 1:
		+
	==Cullin3 - BTB interface: a novel target for stapled peptides==		==Cullin3 - BTB interface: a novel target for stapled peptides==
	<StructureSection load='2myl' size='340' side='right' caption='[[2myl]], [[NMR_Ensembles_of_Models \| 20 NMR models]]' scene=''>		<StructureSection load='2myl' size='340' side='right' caption='[[2myl]], [[NMR_Ensembles_of_Models \| 20 NMR models]]' scene=''>
Line 5:		Line 6:
	</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MK8:2-METHYL-L-NORLEUCINE'>MK8</scene></td></tr>		</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MK8:2-METHYL-L-NORLEUCINE'>MK8</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2mym\|2mym]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2mym\|2mym]]</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=2myl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2myl OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2myl RCSB], [http://www.ebi.ac.uk/pdbsum/2myl 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=2myl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2myl OCA], [http://pdbe.org/2myl PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2myl RCSB], [http://www.ebi.ac.uk/pdbsum/2myl PDBsum]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 19:		Line 20:
	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 2myl" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Cullin\|Cullin]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 12:41, 22 April 2015

OCA — Wed, 22 Apr 2015 12:41:47 GMT

←Older revision		Revision as of 12:41, 22 April 2015
Line 1:		Line 1:
-	'''~~Unreleased~~ structure'''	+	==Cullin3 - BTB interface: a novel target for stapled peptides==
		+	<StructureSection load='2myl' size='340' side='right' caption='[[2myl]], [[NMR_Ensembles_of_Models \| 20 NMR models]]' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[2myl]] is a 1 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2MYL OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2MYL FirstGlance]. <br>
		+	</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MK8:2-METHYL-L-NORLEUCINE'>MK8</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2mym\|2mym]]</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=2myl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2myl OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2myl RCSB], [http://www.ebi.ac.uk/pdbsum/2myl PDBsum]</span></td></tr>
		+	</table>
		+	== Disease ==
		+	[[http://www.uniprot.org/uniprot/CUL3_HUMAN CUL3_HUMAN]] Pseudohypoaldosteronism type 2E. Defects in CUL3 are the cause of Pseudohypoaldosteronism type 2E (PHA2E) [MIM:[http://omim.org/entry/614496 614496]]. An autosomal dominant disorder characterized by severe hypertension, hyperkalemia, hyperchloremia, hyperchloremic metabolic acidosis, and correction of physiologic abnormalities by thiazide diuretics.<ref>PMID:22266938</ref>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/CUL3_HUMAN CUL3_HUMAN]] Core component of multiple cullin-RING-based BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complexes which mediate the ubiquitination and subsequent proteasomal degradation of target proteins. As a scaffold protein may contribute to catalysis through positioning of the substrate and the ubiquitin-conjugating enzyme. The E3 ubiquitin-protein ligase activity of the complex is dependent on the neddylation of the cullin subunit and is inhibited by the association of the deneddylated cullin subunit with TIP120A/CAND1 (By similarity). The functional specificity of the BCR complex depends on the BTB domain-containing protein as the susbstrate recognition component. BCR(SPOP) is involved in ubiquitination of BMI1/PCGF4, H2AFY and DAXX, and probably GLI2 or GLI3. BCR(KLHL9-KLHL13) controls the dynamic behavior of AURKB on mitotic chromosomes and thereby coordinates faithful mitotic progression and completion of cytokinesis. BCR(KLHL12) is involved in ER-Golgi transport by regulating the size of COPII coats, thereby playing a key role in collagen export, which is required for embryonic stem (ES) cells division: BCR(KLHL12) acts by mediating monoubiquitination of SEC31 (SEC31A or SEC31B). BCR(KLHL3) acts as a regulator of ion transport in the distal nephron; possibly by mediating ubiquitination of SLC12A3/NCC. Involved in ubiquitination of cyclin E and of cyclin D1 (in vitro) thus involved in regulation of G1/S transition.<ref>PMID:10500095</ref> <ref>PMID:11311237</ref> <ref>PMID:15897469</ref> <ref>PMID:16524876</ref> <ref>PMID:17543862</ref> <ref>PMID:22358839</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Cullin3 (Cul3), a key factor of protein ubiquitination, is able to interact with dozens of different proteins containing a BTB (Bric-a-brac, Tramtrack and Broad Complex) domain. We here targeted the Cul3-BTB interface by using the intriguing approach of stabilizing the alpha-helical conformation of Cul3-based peptides through the "stapling" with a hydrocarbon cross-linker. In particular, by combining theoretical and experimental techniques, we designed and characterized stapled Cul3-based peptides embedding the helix 2 of the protein (residues 49-68). Intriguingly, CD and NMR experiments demonstrate that these stapled peptides were able to adopt the helical structure that the fragment assumes in the parent protein. We also show that some of these peptides were able to bind to the BTB of the tetrameric KCTD11, a substrate adaptor involved in HDAC1 degradation, with high affinity (~ 300-600 nM). Cul3-derived staple peptides are also able to bind the BTB of the pentameric KCTD5. Interestingly, the affinity of these peptides is of the same order of magnitude of that reported for the interaction of full-length Cul3 with some BTB containing proteins. Moreover, present data indicate that stapling endows these peptides with an increased serum stability. Altogether, these findings indicate that the designed stapled peptides can efficiently mimic protein-protein interactions and are potentially able to modulate fundamental biological processes involving Cul3.

-	~~The entry 2myl is ON HOLD until Paper Publication~~	+	Cullin3 - BTB Interface: A Novel Target for Stapled Peptides.,de Paola I, Pirone L, Palmieri M, Balasco N, Esposito L, Russo L, Mazza D, Di Marcotullio L, Di Gaetano S, Malgieri G, Vitagliano L, Pedone E, Zaccaro L PLoS One. 2015 Apr 7;10(4):e0121149. doi: 10.1371/journal.pone.0121149., eCollection 2015. PMID:25848797<ref>PMID:25848797</ref>

-	~~Authors: Russo~~, L.~~, Palmieri, M~~.~~, Malgieri, G~~.	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-		+	</div>
-	~~Description: Cullin3 -BTB interface: a novel target for stapled peptides~~	+	== References ==
-	[[Category: ~~Unreleased Structures~~]]	+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Malgieri, G]]
	[[Category: Palmieri, M]]		[[Category: Palmieri, M]]
-	[[Category: Malgieri, G]]
	[[Category: Russo, L]]		[[Category: Russo, L]]
		+	[[Category: Protein]]
		+	[[Category: Protein binding]]

OCA at 08:38, 25 February 2015

OCA — Wed, 25 Feb 2015 08:38:50 GMT

←Older revision		Revision as of 08:38, 25 February 2015
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 2myl is ON HOLD	+	The entry 2myl is ON HOLD until Paper Publication

	Authors: Russo, L., Palmieri, M., Malgieri, G.		Authors: Russo, L., Palmieri, M., Malgieri, G.

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

OCA — Sat, 07 Feb 2015 10:54:41 GMT

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

←Older revision

Revision as of 10:54, 7 February 2015

OCA: New page: '''Unreleased structure''' The entry 2myl is ON HOLD Authors: Russo, L., Palmieri, M., Malgieri, G. Description: Cullin3 -BTB interface: a novel target for stapled peptides [[Category:...

OCA — Sat, 07 Feb 2015 10:54:40 GMT

New page: '''Unreleased structure''' The entry 2myl is ON HOLD Authors: Russo, L., Palmieri, M., Malgieri, G. Description: Cullin3 -BTB interface: a novel target for stapled peptides [[Category:...

New page

'''Unreleased structure'''

The entry 2myl is ON HOLD

Authors: Russo, L., Palmieri, M., Malgieri, G.

Description: Cullin3 -BTB interface: a novel target for stapled peptides
[[Category: Unreleased Structures]]
[[Category: Palmieri, M]]
[[Category: Malgieri, G]]
[[Category: Russo, L]]

←Older revision		Revision as of 09:03, 23 February 2022
Line 3:		Line 3:
	<StructureSection load='2myl' size='340' side='right'caption='[[2myl]], [[NMR_Ensembles_of_Models \| 20 NMR models]]' scene=''>		<StructureSection load='2myl' size='340' side='right'caption='[[2myl]], [[NMR_Ensembles_of_Models \| 20 NMR models]]' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[2myl]] is a 1 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2MYL OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=2MYL FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[2myl]] is a 1 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2MYL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2MYL FirstGlance]. <br>
	</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MK8:2-METHYL-L-NORLEUCINE'>MK8</scene></td></tr>		</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MK8:2-METHYL-L-NORLEUCINE'>MK8</scene></td></tr>
-	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2mym\|2mym]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2mym\|2mym]]</div></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=2myl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2myl OCA], [~~http~~://pdbe.org/2myl PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=2myl RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/2myl PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=2myl ProSAT]</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=2myl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2myl OCA], [https://pdbe.org/2myl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2myl RCSB], [https://www.ebi.ac.uk/pdbsum/2myl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2myl ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
-	[[~~http~~://www.uniprot.org/uniprot/CUL3_HUMAN CUL3_HUMAN]] Pseudohypoaldosteronism type 2E. Defects in CUL3 are the cause of Pseudohypoaldosteronism type 2E (PHA2E) [MIM:[~~http~~://omim.org/entry/614496 614496]]. An autosomal dominant disorder characterized by severe hypertension, hyperkalemia, hyperchloremia, hyperchloremic metabolic acidosis, and correction of physiologic abnormalities by thiazide diuretics.<ref>PMID:22266938</ref>	+	[[https://www.uniprot.org/uniprot/CUL3_HUMAN CUL3_HUMAN]] Pseudohypoaldosteronism type 2E. Defects in CUL3 are the cause of Pseudohypoaldosteronism type 2E (PHA2E) [MIM:[https://omim.org/entry/614496 614496]]. An autosomal dominant disorder characterized by severe hypertension, hyperkalemia, hyperchloremia, hyperchloremic metabolic acidosis, and correction of physiologic abnormalities by thiazide diuretics.<ref>PMID:22266938</ref>
	== Function ==		== Function ==
-	[[~~http~~://www.uniprot.org/uniprot/CUL3_HUMAN CUL3_HUMAN]] Core component of multiple cullin-RING-based BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complexes which mediate the ubiquitination and subsequent proteasomal degradation of target proteins. As a scaffold protein may contribute to catalysis through positioning of the substrate and the ubiquitin-conjugating enzyme. The E3 ubiquitin-protein ligase activity of the complex is dependent on the neddylation of the cullin subunit and is inhibited by the association of the deneddylated cullin subunit with TIP120A/CAND1 (By similarity). The functional specificity of the BCR complex depends on the BTB domain-containing protein as the susbstrate recognition component. BCR(SPOP) is involved in ubiquitination of BMI1/PCGF4, H2AFY and DAXX, and probably GLI2 or GLI3. BCR(KLHL9-KLHL13) controls the dynamic behavior of AURKB on mitotic chromosomes and thereby coordinates faithful mitotic progression and completion of cytokinesis. BCR(KLHL12) is involved in ER-Golgi transport by regulating the size of COPII coats, thereby playing a key role in collagen export, which is required for embryonic stem (ES) cells division: BCR(KLHL12) acts by mediating monoubiquitination of SEC31 (SEC31A or SEC31B). BCR(KLHL3) acts as a regulator of ion transport in the distal nephron; possibly by mediating ubiquitination of SLC12A3/NCC. Involved in ubiquitination of cyclin E and of cyclin D1 (in vitro) thus involved in regulation of G1/S transition.<ref>PMID:10500095</ref> <ref>PMID:11311237</ref> <ref>PMID:15897469</ref> <ref>PMID:16524876</ref> <ref>PMID:17543862</ref> <ref>PMID:22358839</ref>	+	[[https://www.uniprot.org/uniprot/CUL3_HUMAN CUL3_HUMAN]] Core component of multiple cullin-RING-based BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complexes which mediate the ubiquitination and subsequent proteasomal degradation of target proteins. As a scaffold protein may contribute to catalysis through positioning of the substrate and the ubiquitin-conjugating enzyme. The E3 ubiquitin-protein ligase activity of the complex is dependent on the neddylation of the cullin subunit and is inhibited by the association of the deneddylated cullin subunit with TIP120A/CAND1 (By similarity). The functional specificity of the BCR complex depends on the BTB domain-containing protein as the susbstrate recognition component. BCR(SPOP) is involved in ubiquitination of BMI1/PCGF4, H2AFY and DAXX, and probably GLI2 or GLI3. BCR(KLHL9-KLHL13) controls the dynamic behavior of AURKB on mitotic chromosomes and thereby coordinates faithful mitotic progression and completion of cytokinesis. BCR(KLHL12) is involved in ER-Golgi transport by regulating the size of COPII coats, thereby playing a key role in collagen export, which is required for embryonic stem (ES) cells division: BCR(KLHL12) acts by mediating monoubiquitination of SEC31 (SEC31A or SEC31B). BCR(KLHL3) acts as a regulator of ion transport in the distal nephron; possibly by mediating ubiquitination of SLC12A3/NCC. Involved in ubiquitination of cyclin E and of cyclin D1 (in vitro) thus involved in regulation of G1/S transition.<ref>PMID:10500095</ref> <ref>PMID:11311237</ref> <ref>PMID:15897469</ref> <ref>PMID:16524876</ref> <ref>PMID:17543862</ref> <ref>PMID:22358839</ref>
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	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==