5n1b - Revision history

OCA at 17:56, 8 November 2023

OCA — Wed, 08 Nov 2023 17:56:51 GMT

←Older revision		Revision as of 17:56, 8 November 2023
Line 1:		Line 1:

	==hPAD4 crystal complex with AFM-14a==		==hPAD4 crystal complex with AFM-14a==
-	<StructureSection load='5n1b' size='340' side='right' caption='[[5n1b]], [[Resolution\|resolution]] 2.90Å' scene=''>	+	<StructureSection load='5n1b' size='340' side='right'caption='[[5n1b]], [[Resolution\|resolution]] 2.90Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5n1b]] is a 1 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=5N1B OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5N1B FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5n1b]] is a 1 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=5N1B OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5N1B FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=8FW:~{N}-[(1~{S})-1-(1~{H}-BENZIMIDAZOL-2-YL)-4-(ETHANIMIDOYLAMINO)BUTYL]-3-OXIDANYLIDENE-ISOINDOLE-4-CARBOXAMIDE'>8FW</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <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]] 2.9Å</td></tr>
-	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5n0m\|5n0m]], [[5n0y\|5n0y]], [[5n0z\|5n0z]]</td></tr>~~	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=8FW:~{N}-[(1~{S})-1-(1~{H}-BENZIMIDAZOL-2-YL)-4-(ETHANIMIDOYLAMINO)BUTYL]-3-OXIDANYLIDENE-ISOINDOLE-4-CARBOXAMIDE'>8FW</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PADI4, PAD4, PADI5, PDI5 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=5n1b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5n1b OCA], [https://pdbe.org/5n1b PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5n1b RCSB], [https://www.ebi.ac.uk/pdbsum/5n1b PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5n1b ProSAT]</span></td></tr>
-	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Protein-arginine_deiminase Protein-arginine deiminase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.3.15 3.5.3.15] </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=5n1b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5n1b OCA], [~~http~~://pdbe.org/5n1b PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5n1b RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5n1b PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5n1b ProSAT]</span></td></tr>	+
	</table>		</table>
	== Disease ==		== Disease ==
-	[~~[http~~://www.uniprot.org/uniprot/PADI4_HUMAN PADI4_HUMAN]] Genetic variations in PADI4 are a cause of susceptibility to rheumatoid arthritis (RA) [MIM:[~~http~~://omim.org/entry/180300 180300]]. It is a systemic inflammatory disease with autoimmune features and a complex genetic component. It primarily affects the joints and is characterized by inflammatory changes in the synovial membranes and articular structures, widespread fibrinoid degeneration of the collagen fibers in mesenchymal tissues, and by atrophy and rarefaction of bony structures. Note=Could have an important role in the pathogenesis of rheumatoid arthritis by increasing citrullination of proteins in rheumatoid arthritis synovial tissues, leading, in a cytokine-rich milieu, to a break in tolerance to citrullinated peptides processed and presented in the appropriate HLA context.<ref>PMID:12833157</ref>	+	[https://www.uniprot.org/uniprot/PADI4_HUMAN PADI4_HUMAN] Genetic variations in PADI4 are a cause of susceptibility to rheumatoid arthritis (RA) [MIM:[https://omim.org/entry/180300 180300]. It is a systemic inflammatory disease with autoimmune features and a complex genetic component. It primarily affects the joints and is characterized by inflammatory changes in the synovial membranes and articular structures, widespread fibrinoid degeneration of the collagen fibers in mesenchymal tissues, and by atrophy and rarefaction of bony structures. Note=Could have an important role in the pathogenesis of rheumatoid arthritis by increasing citrullination of proteins in rheumatoid arthritis synovial tissues, leading, in a cytokine-rich milieu, to a break in tolerance to citrullinated peptides processed and presented in the appropriate HLA context.<ref>PMID:12833157</ref>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/PADI4_HUMAN PADI4_HUMAN]] Catalyzes the citrullination/deimination of arginine residues of proteins. Citrullinates histone H3 at 'Arg-8' and/or 'Arg-17' and histone H4 at 'Arg-3', which prevents their methylation by CARM1 and HRMT1L2/PRMT1 and represses transcription. Citrullinates EP300/P300 at 'Arg-2142', which favors its interaction with NCOA2/GRIP1.<ref>PMID:15339660</ref> <ref>PMID:15345777</ref>	+	[https://www.uniprot.org/uniprot/PADI4_HUMAN PADI4_HUMAN] Catalyzes the citrullination/deimination of arginine residues of proteins. Citrullinates histone H3 at 'Arg-8' and/or 'Arg-17' and histone H4 at 'Arg-3', which prevents their methylation by CARM1 and HRMT1L2/PRMT1 and represses transcription. Citrullinates EP300/P300 at 'Arg-2142', which favors its interaction with NCOA2/GRIP1.<ref>PMID:15339660</ref> <ref>PMID:15345777</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 27:		Line 25:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
-	[[Category: ~~Protein-arginine deiminase~~]]	+	[[Category: Large Structures]]
-	[[Category: Beaumont, E]]	+	[[Category: Beaumont E]]
-	[[Category: Clancy, K]]	+	[[Category: Clancy K]]
-	[[Category: Kerry, P]]	+	[[Category: Kerry P]]
-	[[Category: Muth, A]]	+	[[Category: Muth A]]
-	[[Category: Nagar, M]]	+	[[Category: Nagar M]]
-	[[Category: Parelkar, S]]	+	[[Category: Parelkar S]]
-	[[Category: Srinath, H]]	+	[[Category: Srinath H]]
-	[[Category: Subramanian, V]]	+	[[Category: Subramanian V]]
-	[[Category: Thompson, P]]	+	[[Category: Thompson P]]
-	~~[[Category: Hydrolase-hydrolase inhibitor complex~~]]	+

OCA at 07:27, 29 November 2017

OCA — Wed, 29 Nov 2017 07:27:24 GMT

←Older revision		Revision as of 07:27, 29 November 2017
Line 3:		Line 3:
	<StructureSection load='5n1b' size='340' side='right' caption='[[5n1b]], [[Resolution\|resolution]] 2.90Å' scene=''>		<StructureSection load='5n1b' size='340' side='right' caption='[[5n1b]], [[Resolution\|resolution]] 2.90Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5n1b]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5N1B OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5N1B FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5n1b]] is a 1 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=5N1B OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5N1B FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=8FW:~{N}-[(1~{S})-1-(1~{H}-BENZIMIDAZOL-2-YL)-4-(ETHANIMIDOYLAMINO)BUTYL]-3-OXIDANYLIDENE-ISOINDOLE-4-CARBOXAMIDE'>8FW</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <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=8FW:~{N}-[(1~{S})-1-(1~{H}-BENZIMIDAZOL-2-YL)-4-(ETHANIMIDOYLAMINO)BUTYL]-3-OXIDANYLIDENE-ISOINDOLE-4-CARBOXAMIDE'>8FW</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5n0m\|5n0m]], [[5n0y\|5n0y]], [[5n0z\|5n0z]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PADI4, PAD4, PADI5, PDI5 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Protein-arginine_deiminase Protein-arginine deiminase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.3.15 3.5.3.15] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Protein-arginine_deiminase Protein-arginine deiminase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.3.15 3.5.3.15] </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=5n1b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5n1b OCA], [http://pdbe.org/5n1b PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5n1b RCSB], [http://www.ebi.ac.uk/pdbsum/5n1b PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5n1b 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=5n1b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5n1b OCA], [http://pdbe.org/5n1b PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5n1b RCSB], [http://www.ebi.ac.uk/pdbsum/5n1b PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5n1b ProSAT]</span></td></tr>
Line 25:		Line 27:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Protein-arginine deiminase]]		[[Category: Protein-arginine deiminase]]
	[[Category: Beaumont, E]]		[[Category: Beaumont, E]]

OCA at 13:35, 24 May 2017

OCA — Wed, 24 May 2017 13:35:27 GMT

←Older revision		Revision as of 13:35, 24 May 2017
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 5n1b is ~~ON HOLD~~ ~~until Paper~~ Publication	+	==hPAD4 crystal complex with AFM-14a==
		+	<StructureSection load='5n1b' size='340' side='right' caption='[[5n1b]], [[Resolution\|resolution]] 2.90Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[5n1b]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5N1B OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5N1B FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=8FW:~{N}-[(1~{S})-1-(1~{H}-BENZIMIDAZOL-2-YL)-4-(ETHANIMIDOYLAMINO)BUTYL]-3-OXIDANYLIDENE-ISOINDOLE-4-CARBOXAMIDE'>8FW</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Protein-arginine_deiminase Protein-arginine deiminase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.3.15 3.5.3.15] </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=5n1b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5n1b OCA], [http://pdbe.org/5n1b PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5n1b RCSB], [http://www.ebi.ac.uk/pdbsum/5n1b PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5n1b ProSAT]</span></td></tr>
		+	</table>
		+	== Disease ==
		+	[[http://www.uniprot.org/uniprot/PADI4_HUMAN PADI4_HUMAN]] Genetic variations in PADI4 are a cause of susceptibility to rheumatoid arthritis (RA) [MIM:[http://omim.org/entry/180300 180300]]. It is a systemic inflammatory disease with autoimmune features and a complex genetic component. It primarily affects the joints and is characterized by inflammatory changes in the synovial membranes and articular structures, widespread fibrinoid degeneration of the collagen fibers in mesenchymal tissues, and by atrophy and rarefaction of bony structures. Note=Could have an important role in the pathogenesis of rheumatoid arthritis by increasing citrullination of proteins in rheumatoid arthritis synovial tissues, leading, in a cytokine-rich milieu, to a break in tolerance to citrullinated peptides processed and presented in the appropriate HLA context.<ref>PMID:12833157</ref>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/PADI4_HUMAN PADI4_HUMAN]] Catalyzes the citrullination/deimination of arginine residues of proteins. Citrullinates histone H3 at 'Arg-8' and/or 'Arg-17' and histone H4 at 'Arg-3', which prevents their methylation by CARM1 and HRMT1L2/PRMT1 and represses transcription. Citrullinates EP300/P300 at 'Arg-2142', which favors its interaction with NCOA2/GRIP1.<ref>PMID:15339660</ref> <ref>PMID:15345777</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Protein arginine deiminase 2 (PAD2) plays a key role in the onset and progression of multiple sclerosis, rheumatoid arthritis, and breast cancer. To date, no PAD2-selective inhibitor has been developed. Such a compound will be critical for elucidating the biological roles of this isozyme and may ultimately be useful for treating specific diseases in which PAD2 activity is dysregulated. To achieve this goal, we synthesized a series of benzimidazole-based derivatives of Cl-amidine, hypothesizing that this scaffold would allow access to a series of PAD2-selective inhibitors with enhanced cellular efficacy. Herein, we demonstrate that substitutions at both the N-terminus and C-terminus of Cl-amidine result in >100-fold increases in PAD2 potency and selectivity (30a, 41a, and 49a) as well as cellular efficacy (30a). Notably, these compounds use the far less reactive fluoroacetamidine warhead. In total, we predict that 30a will be a critical tool for understanding cellular PAD2 function and sets the stage for treating diseases in which PAD2 activity is dysregulated.

-	~~Authors: Beaumont, E., Kerry, P., Thompson, P~~., Muth, A., Subramanian, V., Nagar, M., ~~Srinath~~, H., Clancy, K., Parelkar, S.	+	Development of a Selective Inhibitor of Protein Arginine Deiminase 2.,Muth A, Subramanian V, Beaumont E, Nagar M, Kerry P, McEwan P, Srinath H, Clancy K, Parelkar S, Thompson PR J Med Chem. 2017 Apr 13;60(7):3198-3211. doi: 10.1021/acs.jmedchem.7b00274. Epub , 2017 Mar 31. PMID:28328217<ref>PMID:28328217</ref>

-	~~Description: hPAD4 crystal complex with AFM-14a~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[Category: Unreleased Structures]]~~	+	</div>
-	~~[[Category: Parelkar~~, S]]	+	<div class="pdbe-citations 5n1b" style="background-color:#fffaf0;"></div>
-	~~[[Category~~: ~~Srinath, H]]~~	+	== References ==
-	[[Category: ~~Muth, A~~]]	+	<references/>
-	[[Category: ~~Thompson~~, P]]	+	__TOC__
		+	</StructureSection>
		+	[[Category: Protein-arginine deiminase]]
		+	[[Category: Beaumont, E]]
	[[Category: Clancy, K]]		[[Category: Clancy, K]]
-	[[Category: Nagar, M]]
	[[Category: Kerry, P]]		[[Category: Kerry, P]]
		+	[[Category: Muth, A]]
		+	[[Category: Nagar, M]]
		+	[[Category: Parelkar, S]]
		+	[[Category: Srinath, H]]
	[[Category: Subramanian, V]]		[[Category: Subramanian, V]]
-	[[Category: ~~Beaumont~~, E]]	+	[[Category: Thompson, P]]
		+	[[Category: Hydrolase-hydrolase inhibitor complex]]

OCA: Protected "5n1b" [edit=sysop:move=sysop]

OCA — Thu, 09 Mar 2017 11:54:37 GMT

Protected "5n1b" [edit=sysop:move=sysop]

←Older revision

Revision as of 11:54, 9 March 2017

OCA: New page: '''Unreleased structure''' The entry 5n1b is ON HOLD until Paper Publication Authors: Beaumont, E., Kerry, P., Thompson, P., Muth, A., Subramanian, V., Nagar, M., Srinath, H., Clancy, K...

OCA — Thu, 09 Mar 2017 11:54:35 GMT

New page: '''Unreleased structure''' The entry 5n1b is ON HOLD until Paper Publication Authors: Beaumont, E., Kerry, P., Thompson, P., Muth, A., Subramanian, V., Nagar, M., Srinath, H., Clancy, K...

New page

'''Unreleased structure'''

The entry 5n1b is ON HOLD until Paper Publication

Authors: Beaumont, E., Kerry, P., Thompson, P., Muth, A., Subramanian, V., Nagar, M., Srinath, H., Clancy, K., Parelkar, S.

Description: hPAD4 crystal complex with AFM-14a
[[Category: Unreleased Structures]]
[[Category: Parelkar, S]]
[[Category: Srinath, H]]
[[Category: Muth, A]]
[[Category: Thompson, P]]
[[Category: Clancy, K]]
[[Category: Nagar, M]]
[[Category: Kerry, P]]
[[Category: Subramanian, V]]
[[Category: Beaumont, E]]