6tul - Revision history

OCA at 13:09, 24 January 2024

OCA — Wed, 24 Jan 2024 13:09:51 GMT

←Older revision		Revision as of 13:09, 24 January 2024
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	<StructureSection load='6tul' size='340' side='right'caption='[[6tul]], [[Resolution\|resolution]] 2.25Å' scene=''>		<StructureSection load='6tul' size='340' side='right'caption='[[6tul]], [[Resolution\|resolution]] 2.25Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6tul]] 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=6TUL OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=6TUL FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6tul]] 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=6TUL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6TUL FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MLT:D-MALATE'>MLT</scene>, <scene name='pdbligand=P6G:HEXAETHYLENE+GLYCOL'>P6G</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</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]] 2.25Å</td></tr>
-	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[6srv\|6srv]], [[6srx\|6srx]], [[6ss0\|6ss0]], [[6ss2\|6ss2]], [[6ss4\|6ss4]], [[6ss5\|6ss5]], [[6ss6\|6ss6]]</td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MLT:D-MALATE'>MLT</scene>, <scene name='pdbligand=P6G:HEXAETHYLENE+GLYCOL'>P6G</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</scene></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=6tul FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6tul OCA], [~~http~~://pdbe.org/6tul PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6tul RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6tul PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6tul 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=6tul FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6tul OCA], [https://pdbe.org/6tul PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6tul RCSB], [https://www.ebi.ac.uk/pdbsum/6tul PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6tul ProSAT]</span></td></tr>
	</table>		</table>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
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	</div>		</div>
	<div class="pdbe-citations 6tul" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 6tul" 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: Addyman, A]]	+	[[Category: Addyman A]]
-	[[Category: Burschowsky, D]]	+	[[Category: Burschowsky D]]
-	[[Category: Carr, M]]	+	[[Category: Carr M]]
-	[[Category: Fiedler, S]]	+	[[Category: Fiedler S]]
-	[[Category: Groves, M]]	+	[[Category: Groves M]]
-	[[Category: Haynes, S]]	+	[[Category: Haynes S]]
-	[[Category: Seewooruthun, C]]	+	[[Category: Seewooruthun C]]
-	~~[[Category: Antigen-binding fragment]]~~	+
-	~~[[Category: Arginase-2 inhibitor]]~~	+
-	~~[[Category: Igg]]~~	+
-	~~[[Category: Protein binding~~]]	+

OCA at 10:11, 16 September 2020

OCA — Wed, 16 Sep 2020 10:11:34 GMT

←Older revision		Revision as of 10:11, 16 September 2020
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	==Structure of the arginase-2-inhibitory human antigen-binding fragment Fab C0021177==		==Structure of the arginase-2-inhibitory human antigen-binding fragment Fab C0021177==
-	<StructureSection load='6tul' size='340' side='right'caption='[[6tul]]' scene=''>	+	<StructureSection load='6tul' size='340' side='right'caption='[[6tul]], [[Resolution\|resolution]] 2.25Å' 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=6TUL OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6TUL FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6tul]] 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=6TUL OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6TUL 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=6tul FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6tul OCA], [http://pdbe.org/6tul PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6tul RCSB], [http://www.ebi.ac.uk/pdbsum/6tul PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6tul ProSAT]</span></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MLT:D-MALATE'>MLT</scene>, <scene name='pdbligand=P6G:HEXAETHYLENE+GLYCOL'>P6G</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[6srv\|6srv]], [[6srx\|6srx]], [[6ss0\|6ss0]], [[6ss2\|6ss2]], [[6ss4\|6ss4]], [[6ss5\|6ss5]], [[6ss6\|6ss6]]</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=6tul FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6tul OCA], [http://pdbe.org/6tul PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6tul RCSB], [http://www.ebi.ac.uk/pdbsum/6tul PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6tul ProSAT]</span></td></tr>
	</table>		</table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Arginase 2 (ARG2) is a binuclear manganese metalloenzyme that catalyzes the hydrolysis of L-arginine. The dysregulated expression of ARG2 within specific tumor microenvironments generates an immunosuppressive niche that effectively renders the tumor 'invisible' to the host's immune system. Increased ARG2 expression leads to a concomitant depletion of local L-arginine levels, which in turn leads to suppression of anti-tumor T-cell-mediated immune responses. Here we describe the isolation and characterization of a high affinity antibody (C0021158) that inhibits ARG2 enzymatic function completely, effectively restoring T-cell proliferation in vitro. Enzyme kinetic studies confirmed that C0021158 exhibits a noncompetitive mechanism of action, inhibiting ARG2 independently of L-arginine concentrations. To elucidate C0021158's inhibitory mechanism at a structural level, the co-crystal structure of the Fab in complex with trimeric ARG2 was solved. C0021158's epitope was consequently mapped to an area some distance from the enzyme's substrate binding cleft, indicating an allosteric mechanism was being employed. Following C0021158 binding, distinct regions of ARG2 undergo major conformational changes. Notably, the backbone structure of a surface-exposed loop is completely rearranged, leading to the formation of a new short helix structure at the Fab-ARG2 interface. Moreover, this large-scale structural remodeling at ARG2's epitope translates into more subtle changes within the enzyme's active site. An arginine residue at position 39 is reoriented inwards, sterically impeding the binding of L-arginine. Arg39 is also predicted to alter the pK A of a key catalytic histidine residue at position 160, further attenuating ARG2's enzymatic function. In silico molecular docking simulations predict that L-arginine is unable to bind effectively when antibody is bound, a prediction supported by isothermal calorimetry experiments using an L-arginine mimetic. Specifically, targeting ARG2 in the tumor microenvironment through the application of C0021158, potentially in combination with standard chemotherapy regimens or alternate immunotherapies, represents a potential new strategy to target immune cold tumors.
		+
		+	Structural and functional characterization of C0021158, a high-affinity monoclonal antibody that inhibits Arginase 2 function via a novel non-competitive mechanism of action.,Austin M, Burschowsky D, Chan DTY, Jenkinson L, Haynes S, Diamandakis A, Seewooruthun C, Addyman A, Fiedler S, Ryman S, Whitehouse J, Slater LH, Hadjinicolaou AV, Gileadi U, Gowans E, Shibata Y, Barnard M, Kaserer T, Sharma P, Luheshi NM, Wilkinson RW, Vaughan TJ, Holt SV, Cerundolo V, Carr MD, Groves MAT MAbs. 2020 Jan-Dec;12(1):1801230. doi: 10.1080/19420862.2020.1801230. PMID:32880207<ref>PMID:32880207</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 6tul" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Addyman A]]	+	[[Category: Addyman, A]]
-	[[Category: Burschowsky D]]	+	[[Category: Burschowsky, D]]
-	[[Category: Carr M]]	+	[[Category: Carr, M]]
-	[[Category: Fiedler S]]	+	[[Category: Fiedler, S]]
-	[[Category: Groves M]]	+	[[Category: Groves, M]]
-	[[Category: Haynes S]]	+	[[Category: Haynes, S]]
-	[[Category: Seewooruthun C]]	+	[[Category: Seewooruthun, C]]
		+	[[Category: Antigen-binding fragment]]
		+	[[Category: Arginase-2 inhibitor]]
		+	[[Category: Igg]]
		+	[[Category: Protein binding]]

OCA at 06:27, 10 June 2020

OCA — Wed, 10 Jun 2020 06:27:05 GMT

←Older revision		Revision as of 06:27, 10 June 2020
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-	'''Unreleased structure'''

-	~~The entry~~ 6tul is ~~ON HOLD until Paper Publication~~	+	==Structure of the arginase-2-inhibitory human antigen-binding fragment Fab C0021177==
-		+	<StructureSection load='6tul' size='340' side='right'caption='[[6tul]]' scene=''>
-	~~Authors~~:	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6TUL OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6TUL FirstGlance]. <br>
-	~~Description~~:	+	</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=6tul FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6tul OCA], [http://pdbe.org/6tul PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6tul RCSB], [http://www.ebi.ac.uk/pdbsum/6tul PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6tul ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased Structures~~]]	+	</table>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Addyman A]]
		+	[[Category: Burschowsky D]]
		+	[[Category: Carr M]]
		+	[[Category: Fiedler S]]
		+	[[Category: Groves M]]
		+	[[Category: Haynes S]]
		+	[[Category: Seewooruthun C]]

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

OCA — Wed, 22 Jan 2020 13:55:22 GMT

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

←Older revision

Revision as of 13:55, 22 January 2020

OCA: New page: '''Unreleased structure''' The entry 6tul is ON HOLD until Paper Publication Authors: Description: Category: Unreleased Structures

OCA — Wed, 22 Jan 2020 13:55:21 GMT

New page: '''Unreleased structure''' The entry 6tul is ON HOLD until Paper Publication Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 6tul is ON HOLD until Paper Publication

Authors:

Description:
[[Category: Unreleased Structures]]