6ao0 - Revision history

OCA at 14:21, 4 October 2023

OCA — Wed, 04 Oct 2023 14:21:35 GMT

←Older revision		Revision as of 14:21, 4 October 2023
Line 3:		Line 3:
	<StructureSection load='6ao0' size='340' side='right'caption='[[6ao0]], [[Resolution\|resolution]] 2.35Å' scene=''>		<StructureSection load='6ao0' size='340' side='right'caption='[[6ao0]], [[Resolution\|resolution]] 2.35Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6ao0]] is a 2 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=6AO0 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=6AO0 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6ao0]] is a 2 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=6AO0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6AO0 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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]] 2.35Å</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=6ao0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ao0 OCA], [~~http~~://pdbe.org/6ao0 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6ao0 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6ao0 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6ao0 ProSAT]</span></td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=6ao0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ao0 OCA], [https://pdbe.org/6ao0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ao0 RCSB], [https://www.ebi.ac.uk/pdbsum/6ao0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ao0 ProSAT]</span></td></tr>
	</table>		</table>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
Line 16:		Line 17:
	</div>		</div>
	<div class="pdbe-citations 6ao0" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 6ao0" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Monoclonal Antibodies 3D structures\|Monoclonal Antibodies 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Lord~~, D M~~]]	+	[[Category: Lord DM]]
-	[[Category: Wei~~, R R]]~~	+	[[Category: Wei RR]]
-	~~[[Category: Antibody engineering]]~~	+
-	~~[[Category: Fab]]~~	+
-	~~[[Category: Immune system]]~~	+
-	~~[[Category: Protein engineering]]~~	+
-	~~[[Category: Tgf-beta~~]]	+

OCA at 21:29, 28 October 2020

OCA — Wed, 28 Oct 2020 21:29:40 GMT

←Older revision		Revision as of 21:29, 28 October 2020
Line 1:		Line 1:

	==CAT192 Fab Insertion Mutant H2/L2==		==CAT192 Fab Insertion Mutant H2/L2==
-	<StructureSection load='6ao0' size='340' side='right' caption='[[6ao0]], [[Resolution\|resolution]] 2.35Å' scene=''>	+	<StructureSection load='6ao0' size='340' side='right'caption='[[6ao0]], [[Resolution\|resolution]] 2.35Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6ao0]] is a 2 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=6AO0 OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6AO0 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6ao0]] is a 2 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=6AO0 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6AO0 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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=6ao0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ao0 OCA], [http://pdbe.org/6ao0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ao0 RCSB], [http://www.ebi.ac.uk/pdbsum/6ao0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ao0 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=6ao0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ao0 OCA], [http://pdbe.org/6ao0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ao0 RCSB], [http://www.ebi.ac.uk/pdbsum/6ao0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ao0 ProSAT]</span></td></tr>
	</table>		</table>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
Line 21:		Line 21:
	</StructureSection>		</StructureSection>
	[[Category: Human]]		[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Lord, D M]]		[[Category: Lord, D M]]
	[[Category: Wei, R R]]		[[Category: Wei, R R]]

OCA at 07:02, 15 February 2018

OCA — Thu, 15 Feb 2018 07:02:57 GMT

←Older revision		Revision as of 07:02, 15 February 2018
Line 3:		Line 3:
	<StructureSection load='6ao0' size='340' side='right' caption='[[6ao0]], [[Resolution\|resolution]] 2.35Å' scene=''>		<StructureSection load='6ao0' size='340' side='right' caption='[[6ao0]], [[Resolution\|resolution]] 2.35Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6ao0]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6AO0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6AO0 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6ao0]] is a 2 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=6AO0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6AO0 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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=6ao0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ao0 OCA], [http://pdbe.org/6ao0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ao0 RCSB], [http://www.ebi.ac.uk/pdbsum/6ao0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ao0 ProSAT]</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=6ao0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ao0 OCA], [http://pdbe.org/6ao0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ao0 RCSB], [http://www.ebi.ac.uk/pdbsum/6ao0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ao0 ProSAT]</span></td></tr>
Line 20:		Line 20:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Lord, D M]]		[[Category: Lord, D M]]
	[[Category: Wei, R R]]		[[Category: Wei, R R]]

OCA at 05:57, 31 January 2018

OCA — Wed, 31 Jan 2018 05:57:05 GMT

←Older revision		Revision as of 05:57, 31 January 2018
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6ao0 is ~~ON HOLD until Paper~~ Publication	+	==CAT192 Fab Insertion Mutant H2/L2==
		+	<StructureSection load='6ao0' size='340' side='right' caption='[[6ao0]], [[Resolution\|resolution]] 2.35Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[6ao0]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6AO0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6AO0 FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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=6ao0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ao0 OCA], [http://pdbe.org/6ao0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ao0 RCSB], [http://www.ebi.ac.uk/pdbsum/6ao0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ao0 ProSAT]</span></td></tr>
		+	</table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Metelimumab (CAT192) is a human IgG4 monoclonal antibody developed as a TGFbeta1-specific antagonist. It was tested in clinical trials for the treatment of scleroderma but later terminated due to lack of efficacy. Subsequent characterization of CAT192 indicated that its TGFbeta1 binding affinity was reduced by approximately 50-fold upon conversion from the parental single-chain variable fragment (scFv) to IgG4. We hypothesized this result was due to decreased conformational flexibility of the IgG that could be altered via engineering. Therefore, we designed insertion mutants in the elbow region and screened for binding and potency. Our results indicated that increasing the elbow region linker length in each chain successfully restored the isoform-specific and high affinity binding of CAT192 to TGFbeta1. The crystal structure of the high binding affinity mutant displays large conformational rearrangements of the variable domains compared to the wild-type antigen-binding fragment (Fab) and the low binding affinity mutants. Insertion of two glycines in both the heavy and light chain elbow regions provided sufficient flexibility for the variable domains to extend further apart than the wild-type Fab, and allow the CDR3s to make additional interactions not seen in the wild-type Fab structure. These interactions coupled with the dramatic conformational changes provide a possible explanation of how the scFv and elbow-engineered Fabs bind TGFbeta1with high affinity. This study demonstrates the benefits of re-examining both structure and function when converting scFv to IgG molecules, and highlights the potential of structure-based engineering to produce fully functional antibodies.

-	~~Authors:~~ Lord, ~~D.M.~~, Wei, R.R.	+	Structure-based engineering to restore high affinity binding of an isoform-selective anti-TGFbeta1 antibody.,Lord DM, Bird JJ, Honey DM, Best A, Park A, Wei RR, Qiu H MAbs. 2018 Jan 15:0. doi: 10.1080/19420862.2018.1426421. PMID:29333938<ref>PMID:29333938</ref>

-	~~Description~~: ~~CAT192 Fab Insertion Mutant H2~~/L2	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased Structures~~]]	+	</div>
-	[[Category: Wei, R.R]]	+	<div class="pdbe-citations 6ao0" style="background-color:#fffaf0;"></div>
-	[[Category: ~~Lord, D.M~~]]	+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Lord, D M]]
		+	[[Category: Wei, R R]]
		+	[[Category: Antibody engineering]]
		+	[[Category: Fab]]
		+	[[Category: Immune system]]
		+	[[Category: Protein engineering]]
		+	[[Category: Tgf-beta]]

OCA: Protected "6ao0" [edit=sysop:move=sysop]

OCA — Wed, 27 Sep 2017 16:36:26 GMT

Protected "6ao0" [edit=sysop:move=sysop]

←Older revision

Revision as of 16:36, 27 September 2017

OCA: New page: '''Unreleased structure''' The entry 6ao0 is ON HOLD until Paper Publication Authors: Lord, D.M., Wei, R.R. Description: CAT192 Fab Insertion Mutant H2/L2 [[Category: Unreleased Struct...

OCA — Wed, 27 Sep 2017 16:36:25 GMT

New page: '''Unreleased structure''' The entry 6ao0 is ON HOLD until Paper Publication Authors: Lord, D.M., Wei, R.R. Description: CAT192 Fab Insertion Mutant H2/L2 [[Category: Unreleased Struct...

New page

'''Unreleased structure'''

The entry 6ao0 is ON HOLD until Paper Publication

Authors: Lord, D.M., Wei, R.R.

Description: CAT192 Fab Insertion Mutant H2/L2
[[Category: Unreleased Structures]]
[[Category: Wei, R.R]]
[[Category: Lord, D.M]]