8aom - Revision history

OCA at 09:45, 9 October 2024

2024-10-09T09:45:46Z

← Older revision		Revision as of 09:45, 9 October 2024
Line 8:		Line 8:
	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8aom FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8aom OCA], [https://pdbe.org/8aom PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8aom RCSB], [https://www.ebi.ac.uk/pdbsum/8aom PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8aom ProSAT]</span></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=8aom FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8aom OCA], [https://pdbe.org/8aom PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8aom RCSB], [https://www.ebi.ac.uk/pdbsum/8aom PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8aom ProSAT]</span></td></tr>
	</table>		</table>
	== ~~Function~~ ==		<div style="background-color:#fffaf0;">
	~~[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~~>		== Publication Abstract from PubMed ==
			Programmed death-ligand 1 (PD-L1) is a key immune regulatory protein that interacts with programmed cell death protein 1 (PD-1), leading to T-cell suppression. Whilst this interaction is key in self-tolerance, cancer cells evade the immune system by overexpressing PD-L1. Inhibition of the PD-1/PD-L1 pathway with standard monoclonal antibodies has proven a highly effective cancer treatment; however, single domain antibodies (VHH) may offer numerous potential benefits. Here, we report the identification and characterization of a diverse panel of 16 novel VHHs specific to PD-L1. The panel of VHHs demonstrate affinities of 0.7 nM to 5.1 muM and were able to completely inhibit PD-1 binding to PD-L1. The binding site for each VHH on PD-L1 was determined using NMR chemical shift perturbation mapping and revealed a common binding surface encompassing the PD-1-binding site. Additionally, we solved crystal structures of two representative VHHs in complex with PD-L1, which revealed unique binding modes. Similar NMR experiments were used to identify the binding site of CD80 on PD-L1, which is another immune response regulatory element and interacts with PD-L1 localized on the same cell surface. CD80 and PD-1 were revealed to share a highly overlapping binding site on PD-L1, with the panel of VHHs identified expected to inhibit CD80 binding. Comparison of the CD80 and PD-1 binding sites on PD-L1 enabled the identification of a potential antibody binding region able to confer specificity for the inhibition of PD-1 binding only, which may offer therapeutic benefits to counteract cancer cell evasion of the immune system.

			Identification, binding, and structural characterization of single domain anti-PD-L1 antibodies inhibitory of immune regulatory proteins PD-1 and CD80.,Kang-Pettinger T, Walker K, Brown R, Cowan R, Wright H, Baravalle R, Waters LC, Muskett FW, Bowler MW, Sawmynaden K, Coombs PJ, Carr MD, Hall G J Biol Chem. 2023 Jan;299(1):102769. doi: 10.1016/j.jbc.2022.102769. Epub 2022 , Dec 5. PMID:36470427<ref>PMID:36470427</ref>

			From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
			</div>
			<div class="pdbe-citations 8aom" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>

OCA at 08:12, 7 February 2024

2024-02-07T08:12:58Z

← Older revision		Revision as of 08:12, 7 February 2024
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[8aom]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Lama_glama Lama glama]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8AOM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8AOM FirstGlance]. <br>		<table><tr><td colspan='2'>[[8aom]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Lama_glama Lama glama]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8AOM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8AOM FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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]] 2.202Å</td></tr>
			<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=8aom FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8aom OCA], [https://pdbe.org/8aom PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8aom RCSB], [https://www.ebi.ac.uk/pdbsum/8aom PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8aom ProSAT]</span></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=8aom FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8aom OCA], [https://pdbe.org/8aom PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8aom RCSB], [https://www.ebi.ac.uk/pdbsum/8aom PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8aom ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== 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>		[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 ==~~
	Programmed death-ligand 1 (PD-L1) is a key immune regulatory protein that interacts with programmed cell death protein 1 (PD-1), leading to T-cell suppression. Whilst this interaction is key in self-tolerance, cancer cells evade the immune system by overexpressing PD-L1. Inhibition of the PD-1/PD-L1 pathway with standard monoclonal antibodies has proven a highly effective cancer treatment; however, single domain antibodies (VHH) may offer numerous potential benefits. Here, we report the identification and characterization of a diverse panel of 16 novel VHHs specific to PD-L1. The panel of VHHs demonstrate affinities of 0.7 nM to 5.1 muM and were able to completely inhibit PD-1 binding to PD-L1. The binding site for each VHH on PD-L1 was determined using NMR chemical shift perturbation mapping and revealed a common binding surface encompassing the PD-1-binding site. Additionally, we solved crystal structures of two representative VHHs in complex with PD-L1, which revealed unique binding modes. Similar NMR experiments were used to identify the binding site of CD80 on PD-L1, which is another immune response regulatory element and interacts with PD-L1 localized on the same cell surface. CD80 and PD-1 were revealed to share a highly overlapping binding site on PD-L1, with the panel of VHHs identified expected to inhibit CD80 binding. Comparison of the CD80 and PD-1 binding sites on PD-L1 enabled the identification of a potential antibody binding region able to confer specificity for the inhibition of PD-1 binding only, which may offer therapeutic benefits to counteract cancer cell evasion of the immune system.

	Identification, binding, and structural characterization of single domain anti-PD-L1 antibodies inhibitory of immune regulatory proteins PD-1 and CD80.,Kang-Pettinger T, Walker K, Brown R, Cowan R, Wright H, Baravalle R, Waters LC, Muskett FW, Bowler MW, Sawmynaden K, Coombs PJ, Carr MD, Hall G J Biol Chem. 2023 Jan;299(1):102769. doi: 10.1016/j.jbc.2022.102769. Epub 2022 , Dec 5. PMID:36470427<ref>PMID:36470427</ref>

	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~
	~~</div>~~
	~~<div class="pdbe-citations 8aom" style="background-color:#fffaf0;"></div>~~
	== References ==		== References ==
	<references/>		<references/>

OCA at 08:15, 14 June 2023

2023-06-14T08:15:12Z

@@ Line 1: / Line 1: @@
-The entry 8aom is ON HOLD  until Paper Publication
+==Complex of PD-L1 with VHH1==
-Authors:
+Identification, binding, and structural characterization of single domain anti-PD-L1 antibodies inhibitory of immune regulatory proteins PD-1 and CD80.,Kang-Pettinger T, Walker K, Brown R, Cowan R, Wright H, Baravalle R, Waters LC, Muskett FW, Bowler MW, Sawmynaden K, Coombs PJ, Carr MD, Hall G J Biol Chem. 2023 Jan;299(1):102769. doi: 10.1016/j.jbc.2022.102769. Epub 2022 , Dec 5. PMID:36470427<ref>PMID:36470427</ref>
-Description:
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>

OCA at 05:36, 14 September 2022

2022-09-14T05:36:02Z

← Older revision		Revision as of 05:36, 14 September 2022
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

	The entry 8aom is ON HOLD		The entry 8aom is ON HOLD until Paper Publication

	Authors:		Authors:

OCA: Protected "8aom" [edit=sysop:move=sysop]

2022-08-18T03:51:30Z

Protected "8aom" [edit=sysop:move=sysop]

← Older revision	Revision as of 03:51, 18 August 2022
(No difference)

OCA: New page: '''Unreleased structure''' The entry 8aom is ON HOLD Authors: Description: Category: Unreleased Structures

2022-08-18T03:51:28Z

New page: '''Unreleased structure''' The entry 8aom is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 8aom is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]