8do1 - Revision history

OCA at 10:09, 6 September 2023

2023-09-06T10:09:12Z

←Older revision		Revision as of 10:09, 6 September 2023
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	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[8do1]] is a 3 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=8DO1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8DO1 FirstGlance]. <br>		<table><tr><td colspan='2'>[[8do1]] is a 3 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=8DO1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8DO1 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SXF:[(1~{S},3~{R},4~{S},5~{R},6~{R},8~{R},10~{S},23~{R},24~{R},25~{R},26~{R})-5-acetyloxy-6-methyl-4,26-bis(oxidanyl)-17,20-bis(oxidanylidene)-10-pentyl-24-[(~{E})-3-phenylprop-2-enoyl]oxy-2,7,9,21,27-pentaoxatricyclo[21.3.1.0^{3,8}]heptacosan-25-yl]+(~{E})-2-methylbut-2-enoate'>SXF</scene></td></tr>	+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution\|Resolution]] 3.01Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SXF:[(1~{S},3~{R},4~{S},5~{R},6~{R},8~{R},10~{S},23~{R},24~{R},25~{R},26~{R})-5-acetyloxy-6-methyl-4,26-bis(oxidanyl)-17,20-bis(oxidanylidene)-10-pentyl-24-[(~{E})-3-phenylprop-2-enoyl]oxy-2,7,9,21,27-pentaoxatricyclo[21.3.1.0^{3,8}]heptacosan-25-yl]+(~{E})-2-methylbut-2-enoate'>SXF</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=8do1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8do1 OCA], [https://pdbe.org/8do1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8do1 RCSB], [https://www.ebi.ac.uk/pdbsum/8do1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8do1 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=8do1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8do1 OCA], [https://pdbe.org/8do1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8do1 RCSB], [https://www.ebi.ac.uk/pdbsum/8do1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8do1 ProSAT]</span></td></tr>
	</table>		</table>

OCA at 04:04, 25 May 2023

2023-05-25T04:04:10Z

←Older revision		Revision as of 04:04, 25 May 2023
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-	'''Unreleased structure'''

-	~~The entry~~ 8do1 is ~~ON HOLD~~ ~~until Paper~~ Publication	+	==Cryo-EM structure of the human Sec61 complex inhibited by ipomoeassin F==
		+	<StructureSection load='8do1' size='340' side='right'caption='[[8do1]], [[Resolution\|resolution]] 3.01Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[8do1]] is a 3 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=8DO1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8DO1 FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SXF:[(1~{S},3~{R},4~{S},5~{R},6~{R},8~{R},10~{S},23~{R},24~{R},25~{R},26~{R})-5-acetyloxy-6-methyl-4,26-bis(oxidanyl)-17,20-bis(oxidanylidene)-10-pentyl-24-[(~{E})-3-phenylprop-2-enoyl]oxy-2,7,9,21,27-pentaoxatricyclo[21.3.1.0^{3,8}]heptacosan-25-yl]+(~{E})-2-methylbut-2-enoate'>SXF</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=8do1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8do1 OCA], [https://pdbe.org/8do1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8do1 RCSB], [https://www.ebi.ac.uk/pdbsum/8do1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8do1 ProSAT]</span></td></tr>
		+	</table>
		+	== Disease ==
		+	[https://www.uniprot.org/uniprot/S61A1_HUMAN S61A1_HUMAN] The disease is caused by variants affecting the gene represented in this entry. Defects in SEC61A1 may be a cause of autosomal dominant hypogammaglobulinemia, resulting in severe recurrent infections, mainly of the respiratory tract. Disease onset is mostly in the first year of life. Affected subjects manifest reduced antibodies production by plasma cells, in the presence of normal subpopulations of B and T cells in the peripheral blood. Patients respond well to immunoglobulin replacement therapy.<ref>PMID:28782633</ref>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/S61A1_HUMAN S61A1_HUMAN] Component of SEC61 channel-forming translocon complex that mediates transport of signal peptide-containing precursor polypeptides across the endoplasmic reticulum (ER) (PubMed:12475939, PubMed:22375059, PubMed:28782633, PubMed:29719251, PubMed:32814900). Forms a ribosome receptor and a gated pore in the ER membrane, both functions required for cotranslational translocation of nascent polypeptides (PubMed:22375059, PubMed:28782633, PubMed:29719251). May cooperate with auxiliary protein SEC62, SEC63 and HSPA5/BiP to enable post-translational transport of small presecretory proteins (PubMed:22375059, PubMed:29719251). The SEC61 channel is also involved in ER membrane insertion of transmembrane proteins: it mediates membrane insertion of the first few transmembrane segments of proteins, while insertion of subsequent transmembrane regions of multi-pass membrane proteins is mediated by the multi-pass translocon (MPT) complex (PubMed:32820719, PubMed:36261522). The SEC61 channel cooperates with the translocating protein TRAM1 to import nascent proteins into the ER (PubMed:8616892). Controls the passive efflux of calcium ions from the ER lumen to the cytosol through SEC61 channel, contributing to the maintenance of cellular calcium homeostasis (PubMed:28782633). Plays a critical role in nephrogenesis, specifically at pronephros stage (By similarity).[UniProtKB:P61620]<ref>PMID:12475939</ref> <ref>PMID:22375059</ref> <ref>PMID:28782633</ref> <ref>PMID:29719251</ref> <ref>PMID:32814900</ref> <ref>PMID:32820719</ref> <ref>PMID:36261522</ref> <ref>PMID:8616892</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The Sec61 complex forms a protein-conducting channel in the endoplasmic reticulum membrane that is required for secretion of soluble proteins and production of many membrane proteins. Several natural and synthetic small molecules specifically inhibit Sec61, generating cellular effects that are useful for therapeutic purposes, but their inhibitory mechanisms remain unclear. Here we present near-atomic-resolution structures of human Sec61 inhibited by a comprehensive panel of structurally distinct small molecules-cotransin, decatransin, apratoxin, ipomoeassin, mycolactone, cyclotriazadisulfonamide and eeyarestatin. All inhibitors bind to a common lipid-exposed pocket formed by the partially open lateral gate and plug domain of Sec61. Mutations conferring resistance to the inhibitors are clustered at this binding pocket. The structures indicate that Sec61 inhibitors stabilize the plug domain in a closed state, thereby preventing the protein-translocation pore from opening. Our study provides the atomic details of Sec61-inhibitor interactions and the structural framework for further pharmacological studies and drug design.

-	~~Authors~~:	+	A common mechanism of Sec61 translocon inhibition by small molecules.,Itskanov S, Wang L, Junne T, Sherriff R, Xiao L, Blanchard N, Shi WQ, Forsyth C, Hoepfner D, Spiess M, Park E Nat Chem Biol. 2023 May 11. doi: 10.1038/s41589-023-01337-y. PMID:37169959<ref>PMID:37169959</ref>

-	~~Description~~:	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased~~ Structures]]	+	</div>
		+	<div class="pdbe-citations 8do1" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Homo sapiens]]
		+	[[Category: Large Structures]]
		+	[[Category: Itskanov S]]
		+	[[Category: Park E]]

OCA at 04:03, 18 August 2022

2022-08-18T04:03:13Z

←Older revision		Revision as of 04:03, 18 August 2022
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 8do1 is ON HOLD	+	The entry 8do1 is ON HOLD until Paper Publication

	Authors:		Authors:

OCA: Protected "8do1" [edit=sysop:move=sysop]

2022-07-20T04:33:59Z

Protected "8do1" [edit=sysop:move=sysop]

←Older revision

Revision as of 04:33, 20 July 2022

OCA: New page: '''Unreleased structure''' The entry 8do1 is ON HOLD Authors: Description: Category: Unreleased Structures

2022-07-20T04:33:57Z

New page: '''Unreleased structure''' The entry 8do1 is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 8do1 is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]