7sjq - Revision history

OCA at 16:52, 18 October 2023

OCA — Wed, 18 Oct 2023 16:52:22 GMT

←Older revision		Revision as of 16:52, 18 October 2023
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-	====	+	==Ex silico engineering of cystine-dense peptides yielding a potent bispecific T-cell engager==
-	<StructureSection load='7sjq' size='340' side='right'caption='[[7sjq]]' scene=''>	+	<StructureSection load='7sjq' size='340' side='right'caption='[[7sjq]], [[Resolution\|resolution]] 2.00Å' 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'>[[7sjq]] is a 2 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=7SJQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7SJQ 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=7sjq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7sjq OCA], [https://pdbe.org/7sjq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7sjq RCSB], [https://www.ebi.ac.uk/pdbsum/7sjq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7sjq 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]] 2Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <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=7sjq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7sjq OCA], [https://pdbe.org/7sjq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7sjq RCSB], [https://www.ebi.ac.uk/pdbsum/7sjq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7sjq ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/PD1L1_HUMAN PD1L1_HUMAN] Involved in the costimulatory signal, essential for T-cell proliferation and production of IL10 and IFNG, in an IL2-dependent and a PDCD1-independent manner. Interaction with PDCD1 inhibits T-cell proliferation and cytokine production.<ref>PMID:10581077</ref> <ref>PMID:11015443</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Cystine-dense peptides (CDPs) are a miniprotein class that can drug difficult targets with high affinity and low immunogenicity. Tools for their design, however, are not as developed as those for small-molecule and antibody drugs. CDPs have diverse taxonomic origins, but structural characterization is lacking. Here, we adapted Iterative Threading ASSEmbly Refinement (I-TASSER) and Rosetta protein modeling software for structural prediction of 4298 CDP scaffolds and performed in silico prescreening for CDP binders to targets of interest. Mammalian display screening of a library of docking-enriched, methionine and tyrosine scanned (DEMYS) CDPs against PD-L1 yielded binders from four distinct CDP scaffolds. One was affinity-matured, and cocrystallography yielded a high-affinity (KD = 202 pM) PD-L1-binding CDP that competes with PD-1 for PD-L1 binding. Its subsequent incorporation into a CD3-binding bispecific T cell engager produced a molecule with pM-range in vitro T cell killing potency and which substantially extends survival in two different xenograft tumor-bearing mouse models. Both in vitro and in vivo, the CDP-incorporating bispecific molecule outperformed a comparator antibody-based molecule. This CDP modeling and DEMYS technique can accelerate CDP therapeutic development.
		+
		+	Ex silico engineering of cystine-dense peptides yielding a potent bispecific T cell engager.,Crook ZR, Girard EJ, Sevilla GP, Brusniak MY, Rupert PB, Friend DJ, Gewe MM, Clarke M, Lin I, Ruff R, Pakiam F, Phi TD, Bandaranayake A, Correnti CE, Mhyre AJ, Nairn NW, Strong RK, Olson JM Sci Transl Med. 2022 May 18;14(645):eabn0402. doi: 10.1126/scitranslmed.abn0402. , Epub 2022 May 18. PMID:35584229<ref>PMID:35584229</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7sjq" 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: Rupert PB]]
		+	[[Category: Strong R]]

OCA at 05:29, 8 June 2022

OCA — Wed, 08 Jun 2022 05:29:55 GMT

←Older revision		Revision as of 05:29, 8 June 2022
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-	'''Unreleased structure'''

-	~~The entry~~ 7sjq ~~is ON HOLD until Paper Publication~~	+	====
-		+	<StructureSection load='7sjq' size='340' side='right'caption='[[7sjq]]' scene=''>
-	~~Authors~~: ~~Rupert, P~~.B.~~, Strong, R~~.	+	== 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: Ex silico engineering of cystine~~-~~dense peptides yielding~~ a ~~potent bispecific T-cell engager~~	+	</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=7sjq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7sjq OCA], [https://pdbe.org/7sjq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7sjq RCSB], [https://www.ebi.ac.uk/pdbsum/7sjq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7sjq ProSAT]</span></td></tr>
-	[[~~Category~~: ~~Unreleased Structures~~]]	+	</table>
-	[[~~Category~~: ~~Rupert~~, P.B]]	+	__TOC__
-	[[Category: ~~Strong, R~~]]	+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Z-disk]]

OCA at 10:55, 24 November 2021

OCA — Wed, 24 Nov 2021 10:55:39 GMT

←Older revision		Revision as of 10:55, 24 November 2021
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 7sjq is ON HOLD	+	The entry 7sjq is ON HOLD until Paper Publication

	Authors: Rupert, P.B., Strong, R.		Authors: Rupert, P.B., Strong, R.
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	Description: Ex silico engineering of cystine-dense peptides yielding a potent bispecific T-cell engager		Description: Ex silico engineering of cystine-dense peptides yielding a potent bispecific T-cell engager
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
-	[[Category: Strong, R]]
	[[Category: Rupert, P.B]]		[[Category: Rupert, P.B]]
		+	[[Category: Strong, R]]

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

OCA — Wed, 27 Oct 2021 12:45:57 GMT

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

←Older revision

Revision as of 12:45, 27 October 2021

OCA: New page: '''Unreleased structure''' The entry 7sjq is ON HOLD Authors: Rupert, P.B., Strong, R. Description: Ex silico engineering of cystine-dense peptides yielding a potent bispecific T-cell ...

OCA — Wed, 27 Oct 2021 12:45:56 GMT

New page: '''Unreleased structure''' The entry 7sjq is ON HOLD Authors: Rupert, P.B., Strong, R. Description: Ex silico engineering of cystine-dense peptides yielding a potent bispecific T-cell ...

New page

'''Unreleased structure'''

The entry 7sjq is ON HOLD

Authors: Rupert, P.B., Strong, R.

Description: Ex silico engineering of cystine-dense peptides yielding a potent bispecific T-cell engager
[[Category: Unreleased Structures]]
[[Category: Strong, R]]
[[Category: Rupert, P.B]]