6nov - Revision history

OCA at 17:26, 14 August 2019

OCA — Wed, 14 Aug 2019 17:26:56 GMT

←Older revision		Revision as of 17:26, 14 August 2019
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	<StructureSection load='6nov' size='340' side='right'caption='[[6nov]], [[Resolution\|resolution]] 2.14Å' scene=''>		<StructureSection load='6nov' size='340' side='right'caption='[[6nov]], [[Resolution\|resolution]] 2.14Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6nov]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6NOV OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6NOV FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6nov]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6NOV OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6NOV FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=12P:DODECAETHYLENE+GLYCOL'>12P</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=12P:DODECAETHYLENE+GLYCOL'>12P</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[6nou\|6nou]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[6nou\|6nou]]</td></tr>
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Atwell, S]]		[[Category: Atwell, S]]

OCA at 06:03, 19 June 2019

OCA — Wed, 19 Jun 2019 06:03:56 GMT

←Older revision		Revision as of 06:03, 19 June 2019
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-	'''Unreleased structure'''

-	~~The entry~~ 6nov is ~~ON HOLD~~	+	==A Fab derived from ixekizumab==
		+	<StructureSection load='6nov' size='340' side='right'caption='[[6nov]], [[Resolution\|resolution]] 2.14Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[6nov]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6NOV OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6NOV FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=12P:DODECAETHYLENE+GLYCOL'>12P</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[6nou\|6nou]]</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=6nov FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6nov OCA], [http://pdbe.org/6nov PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6nov RCSB], [http://www.ebi.ac.uk/pdbsum/6nov PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6nov ProSAT]</span></td></tr>
		+	</table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	We describe a bispecific dual-antagonist antibody against human B cell activating factor (BAFF) and interleukin 17A (IL-17). An anti-IL-17 single-chain variable fragment (scFv) derived from ixekizumab (Taltz(R)) was fused via a glycine-rich linker to anti-BAFF tabalumab. The IgG-scFv bound both BAFF and IL-17 simultaneously with identical stoichiometry as the parental mAbs. Stability studies of the initial IgG-scFv revealed chemical degradation and aggregation not observed in either parental antibody. The anti-IL-17 scFv showed a high melting temperature (Tm) by differential scanning calorimetry (73.1 degrees C), but also concentration-dependent, initially reversible, protein self-association. To engineer scFv stability, three parallel approaches were taken: labile complementary-determining region (CDR) residues were replaced by stable, affinity-neutral amino acids, CDR charge distribution was balanced, and a H44-L100 interface disulfide bond was introduced. The Tm of the disulfide-stabilized scFv was largely unperturbed, yet it remained monodispersed at high protein concentration. Fluorescent dye binding titrations indicated reduced solvent exposure of hydrophobic residues and decreased proteolytic susceptibility was observed, both indicative of enhanced conformational stability. Superimposition of the H44-L100 scFv (PDB id: 6NOU) and ixekizumab antigen-binding fragment (PDB id: 6NOV) crystal structures revealed nearly identical orientation of the frameworks and CDR loops. The stabilized bispecific molecule LY3090106 (tibulizumab) potently antagonized both BAFF and IL-17 in cell-based and in vivo mouse models. In cynomolgus monkey, it suppressed B cell development and survival and remained functionally intact in circulation, with a prolonged half-life. In summary, we engineered a potent bispecific antibody targeting two key cytokines involved in human autoimmunity amenable to clinical development.

-	~~Authors~~:	+	Development of tibulizumab, a tetravalent bispecific antibody targeting BAFF and IL-17A for the treatment of autoimmune disease.,Benschop RJ, Chow CK, Tian Y, Nelson J, Barmettler B, Atwell S, Clawson D, Chai Q, Jones B, Fitchett J, Torgerson S, Ji Y, Bina H, Hu N, Ghanem M, Manetta J, Wroblewski VJ, Lu J, Allan BW MAbs. 2019 Jun 10:1-16. doi: 10.1080/19420862.2019.1624463. PMID:31181988<ref>PMID:31181988</ref>

-	~~Description~~:	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased~~ Structures]]	+	</div>
		+	<div class="pdbe-citations 6nov" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Atwell, S]]
		+	[[Category: Clawson, D K]]
		+	[[Category: Durbin, J D]]
		+	[[Category: Lu, F]]
		+	[[Category: Lu, J]]
		+	[[Category: Schmitt, M]]
		+	[[Category: Tian, Y]]
		+	[[Category: Antibody]]
		+	[[Category: Fab]]
		+	[[Category: Il-17]]
		+	[[Category: Il17]]
		+	[[Category: Immune system]]
		+	[[Category: Ixekizumab]]

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

OCA — Wed, 30 Jan 2019 06:41:26 GMT

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

←Older revision

Revision as of 06:41, 30 January 2019

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

OCA — Wed, 30 Jan 2019 06:41:25 GMT

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

New page

'''Unreleased structure'''

The entry 6nov is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]