6zl1 - Revision history

OCA at 11:53, 1 February 2024

OCA — Thu, 01 Feb 2024 11:53:57 GMT

←Older revision		Revision as of 11:53, 1 February 2024
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-	====	+	==Crystal structure of human serum albumin in complex with the MCL-1 neutralizing Alphabody CMPX-383B==
-	<StructureSection load='6zl1' size='340' side='right'caption='[[6zl1]]' scene=''>	+	<StructureSection load='6zl1' size='340' side='right'caption='[[6zl1]], [[Resolution\|resolution]] 3.27Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6zl1]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6ZL1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6ZL1 FirstGlance]. <br>
-	</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=6zl1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6zl1 OCA], [https://pdbe.org/6zl1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6zl1 RCSB], [https://www.ebi.ac.uk/pdbsum/6zl1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6zl1 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]] 3.272Å</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=6zl1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6zl1 OCA], [https://pdbe.org/6zl1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6zl1 RCSB], [https://www.ebi.ac.uk/pdbsum/6zl1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6zl1 ProSAT]</span></td></tr>
	</table>		</table>
		+	== Disease ==
		+	[https://www.uniprot.org/uniprot/ALBU_HUMAN ALBU_HUMAN] Defects in ALB are a cause of familial dysalbuminemic hyperthyroxinemia (FDH) [MIM:[https://omim.org/entry/103600 103600]. FDH is a form of euthyroid hyperthyroxinemia that is due to increased affinity of ALB for T(4). It is the most common cause of inherited euthyroid hyperthyroxinemia in Caucasian population.<ref>PMID:8048949</ref> <ref>PMID:7852505</ref> <ref>PMID:9329347</ref> <ref>PMID:9589637</ref>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/ALBU_HUMAN ALBU_HUMAN] Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloidal osmotic pressure of blood. Major zinc transporter in plasma, typically binds about 80% of all plasma zinc.<ref>PMID:19021548</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The therapeutic scope of antibody and nonantibody protein scaffolds is still prohibitively limited against intracellular drug targets. Here, we demonstrate that the Alphabody scaffold can be engineered into a cell-penetrating protein antagonist against induced myeloid leukemia cell differentiation protein MCL-1, an intracellular target in cancer, by grafting the critical B-cell lymphoma 2 homology 3 helix of MCL-1 onto the Alphabody and tagging the scaffold's termini with designed cell-penetration polypeptides. Introduction of an albumin-binding moiety extended the serum half-life of the engineered Alphabody to therapeutically relevant levels, and administration thereof in mouse tumor xenografts based on myeloma cell lines reduced tumor burden. Crystal structures of such a designed Alphabody in complex with MCL-1 and serum albumin provided the structural blueprint of the applied design principles. Collectively, we provide proof of concept for the use of Alphabodies against intracellular disease mediators, which, to date, have remained in the realm of small-molecule therapeutics.
		+
		+	Cell-penetrating Alphabody protein scaffolds for intracellular drug targeting.,Pannecoucke E, Van Trimpont M, Desmet J, Pieters T, Reunes L, Demoen L, Vuylsteke M, Loverix S, Vandenbroucke K, Alard P, Henderikx P, Deroo S, Baatz F, Lorent E, Thiolloy S, Somers K, McGrath Y, Van Vlierberghe P, Lasters I, Savvides SN Sci Adv. 2021 Mar 26;7(13):eabe1682. doi: 10.1126/sciadv.abe1682. Print 2021 Mar. PMID:33771865<ref>PMID:33771865</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 6zl1" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: ~~Z-disk~~]]	+	[[Category: Synthetic construct]]
		+	[[Category: Desmet J]]
		+	[[Category: Lasters I]]
		+	[[Category: Pannecoucke E]]
		+	[[Category: Savvides SN]]

OCA at 05:18, 28 April 2021

OCA — Wed, 28 Apr 2021 05:18:40 GMT

←Older revision		Revision as of 05:18, 28 April 2021
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-	'''Unreleased structure'''

-	~~The entry~~ 6zl1 ~~is ON HOLD until Paper Publication~~	+	====
-		+	<StructureSection load='6zl1' size='340' side='right'caption='[[6zl1]]' scene=''>
-	~~Authors~~:	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br>
-	~~Description~~:	+	</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=6zl1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6zl1 OCA], [https://pdbe.org/6zl1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6zl1 RCSB], [https://www.ebi.ac.uk/pdbsum/6zl1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6zl1 ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	</table>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Z-disk]]

OCA at 05:55, 21 April 2021

OCA — Wed, 21 Apr 2021 05:55:06 GMT

←Older revision		Revision as of 05:55, 21 April 2021
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6zl1 is ON HOLD	+	The entry 6zl1 is ON HOLD until Paper Publication

	Authors:		Authors:

OCA at 05:31, 14 April 2021

OCA — Wed, 14 Apr 2021 05:31:09 GMT

←Older revision		Revision as of 05:31, 14 April 2021
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6zl1 is ON HOLD ~~until Paper Publication~~	+	The entry 6zl1 is ON HOLD

	Authors:		Authors:

OCA at 08:00, 22 July 2020

OCA — Wed, 22 Jul 2020 08:00:49 GMT

←Older revision		Revision as of 08:00, 22 July 2020
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6zl1 is ON HOLD	+	The entry 6zl1 is ON HOLD until Paper Publication

	Authors:		Authors:

OCA: Protected "6zl1" [edit=sysop:move=sysop]

OCA — Wed, 08 Jul 2020 11:17:12 GMT

Protected "6zl1" [edit=sysop:move=sysop]

←Older revision

Revision as of 11:17, 8 July 2020

OCA: New page: '''Unreleased structure''' The entry 6zl1 is ON HOLD Authors: Description: Category: Unreleased Structures

OCA — Wed, 08 Jul 2020 11:17:11 GMT

New page: '''Unreleased structure''' The entry 6zl1 is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 6zl1 is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]