7kqy - Revision history

OCA at 15:30, 18 October 2023

OCA — Wed, 18 Oct 2023 15:30:28 GMT

←Older revision		Revision as of 15:30, 18 October 2023
Line 1:		Line 1:

	==Crystal Structure and Characterization of Human Heavy-Chain only Antibodies reveals a novel, stable dimeric structure similar to Monoclonal Antibodies==		==Crystal Structure and Characterization of Human Heavy-Chain only Antibodies reveals a novel, stable dimeric structure similar to Monoclonal Antibodies==
-	<StructureSection load='7kqy' size='340' side='right'caption='[[7kqy]]' scene=''>	+	<StructureSection load='7kqy' size='340' side='right'caption='[[7kqy]], [[Resolution\|resolution]] 2.91Å' 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=7KQY OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=7KQY FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7kqy]] is a 6 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=7KQY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7KQY FirstGlance]. <br>
-	</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=7kqy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7kqy OCA], [~~http~~://pdbe.org/7kqy PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=7kqy RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/7kqy PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=7kqy 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]] 2.913Å</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=7kqy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7kqy OCA], [https://pdbe.org/7kqy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7kqy RCSB], [https://www.ebi.ac.uk/pdbsum/7kqy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7kqy ProSAT]</span></td></tr>
	</table>		</table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	We report the novel crystal structure and characterization of symmetrical, homodimeric humanized heavy-chain-only antibodies or dimers (HC2s). HC2s were found to be significantly coexpressed and secreted along with mAbs from transient CHO HC/LC cotransfection, resulting in an unacceptable mAb developability attribute. Expression of full-length HC2s in the absence of LC followed by purification resulted in HC2s with high purity and thermal stability similar to conventional mAbs. The VH and CH1 portion of the heavy chain (or Fd) was also efficiently expressed and yielded a stable, covalent, and reducible dimer (Fd2). Mutagenesis of all heavy chain cysteines involved in disulfide bond formation revealed that Fd2 intermolecular disulfide formation was similar to Fabs and elucidated requirements for Fd2 folding and expression. For one HC2, we solved the crystal structure of the Fd2 domain to 2.9 A, revealing a highly symmetrical homodimer that is structurally similar to Fabs and is mediated by conserved (CH1) and variable (VH) contacts with all CDRs positioned outward for target binding. Interfacial dimer contacts revealed by the crystal structure were mutated for two HC2s and were found to dramatically affect HC2 formation while maintaining mAb bioactivity, offering a potential means to modulate novel HC2 formation through engineering. These findings indicate that human heavy-chain dimers can be secreted efficiently in the absence of light chains, may show good physicochemical properties and stability, are structurally similar to Fabs, offer insights into their mechanism of formation, and may be amenable as a novel therapeutic modality.
		+
		+	Crystal Structure and Characterization of Human Heavy-Chain Only Antibodies Reveals a Novel, Stable Dimeric Structure Similar to Monoclonal Antibodies.,Mieczkowski C, Bahmanjah S, Yu Y, Baker J, Raghunathan G, Tomazela D, Hsieh M, McCoy M, Strickland C, Fayadat-Dilman L Antibodies (Basel). 2020 Nov 22;9(4). pii: antib9040066. doi:, 10.3390/antib9040066. PMID:33266498<ref>PMID:33266498</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7kqy" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Bahmanjah S]]		[[Category: Bahmanjah S]]

OCA at 12:37, 16 December 2020

OCA — Wed, 16 Dec 2020 12:37:22 GMT

←Older revision		Revision as of 12:37, 16 December 2020
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry 7kqy is ON HOLD~~	+	==Crystal Structure and Characterization of Human Heavy-Chain only Antibodies reveals a novel, stable dimeric structure similar to Monoclonal Antibodies==
-		+	<StructureSection load='7kqy' size='340' side='right'caption='[[7kqy]]' scene=''>
-	~~Authors: Bahmanjah, S., Mieczkowski, C., Yu, Y., Baker, J., Raghunathan, G., Tomazela, D., Hsieh, M., Mccoy, M., Strickland, C., Fayadat-Dilman, L.~~	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7KQY OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=7KQY FirstGlance]. <br>
-	~~Description:~~ Crystal Structure and Characterization of Human Heavy-Chain only Antibodies reveals a novel, stable dimeric structure similar to Monoclonal Antibodies	+	</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=7kqy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7kqy OCA], [http://pdbe.org/7kqy PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=7kqy RCSB], [http://www.ebi.ac.uk/pdbsum/7kqy PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=7kqy ProSAT]</span></td></tr>
-	[[~~Category: Unreleased Structures~~]]	+	</table>
-	[[~~Category~~: ~~Hsieh, M]~~]	+	__TOC__
-	[[~~Category~~: ~~Mccoy~~, M]]	+	</StructureSection>
-	[[Category: ~~Yu, Y~~]]	+	[[Category: Large Structures]]
-	[[Category: Bahmanjah, S]]	+	[[Category: Bahmanjah S]]
-	[[Category: Baker, J]]	+	[[Category: Baker J]]
-	[[Category: ~~Tomazela, D~~]]	+	[[Category: Fayadat-Dilman L]]
-	[[Category: ~~Fayadat-Dilman, L~~]]	+	[[Category: Hsieh M]]
-	[[Category: Mieczkowski, C]]	+	[[Category: Mccoy M]]
-	[[Category: Raghunathan, G]]	+	[[Category: Mieczkowski C]]
-	[[Category: Strickland, C]]	+	[[Category: Raghunathan G]]
		+	[[Category: Strickland C]]
		+	[[Category: Tomazela D]]
		+	[[Category: Yu Y]]

OCA: Protected "7kqy" [edit=sysop:move=sysop]

OCA — Wed, 25 Nov 2020 05:34:08 GMT

Protected "7kqy" [edit=sysop:move=sysop]

←Older revision

Revision as of 05:34, 25 November 2020

OCA: New page: '''Unreleased structure''' The entry 7kqy is ON HOLD Authors: Bahmanjah, S., Mieczkowski, C., Yu, Y., Baker, J., Raghunathan, G., Tomazela, D., Hsieh, M., Mccoy, M., Strickland, C., Fay...

OCA — Wed, 25 Nov 2020 05:34:07 GMT

New page: '''Unreleased structure''' The entry 7kqy is ON HOLD Authors: Bahmanjah, S., Mieczkowski, C., Yu, Y., Baker, J., Raghunathan, G., Tomazela, D., Hsieh, M., Mccoy, M., Strickland, C., Fay...

New page

'''Unreleased structure'''

The entry 7kqy is ON HOLD

Authors: Bahmanjah, S., Mieczkowski, C., Yu, Y., Baker, J., Raghunathan, G., Tomazela, D., Hsieh, M., Mccoy, M., Strickland, C., Fayadat-Dilman, L.

Description: Crystal Structure and Characterization of Human Heavy-Chain only Antibodies reveals a novel, stable dimeric structure similar to Monoclonal Antibodies
[[Category: Unreleased Structures]]
[[Category: Hsieh, M]]
[[Category: Mccoy, M]]
[[Category: Yu, Y]]
[[Category: Bahmanjah, S]]
[[Category: Baker, J]]
[[Category: Tomazela, D]]
[[Category: Fayadat-Dilman, L]]
[[Category: Mieczkowski, C]]
[[Category: Raghunathan, G]]
[[Category: Strickland, C]]