5r8e - Revision history

OCA at 11:37, 21 February 2024

OCA — Wed, 21 Feb 2024 11:37:31 GMT

←Older revision		Revision as of 11:37, 21 February 2024
Line 3:		Line 3:
	<StructureSection load='5r8e' size='340' side='right'caption='[[5r8e]], [[Resolution\|resolution]] 1.35Å' scene=''>		<StructureSection load='5r8e' size='340' side='right'caption='[[5r8e]], [[Resolution\|resolution]] 1.35Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5r8e]] 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=5R8E OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=5R8E FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5r8e]] 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=5R8E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5R8E FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=S7S:~{N}-(2-ethyl-1,2,3,4-tetrazol-5-yl)butanamide'>S7S</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]] 1.35Å</td></tr>
-	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">IL1B, IL1F2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])~~</td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=S7S:~{N}-(2-ethyl-1,2,3,4-tetrazol-5-yl)butanamide'>S7S</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'>[~~http~~://proteopedia.org/fgij/fg.htm?mol=5r8e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5r8e OCA], [~~http~~://pdbe.org/5r8e PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5r8e RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5r8e PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5r8e 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=5r8e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5r8e OCA], [https://pdbe.org/5r8e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5r8e RCSB], [https://www.ebi.ac.uk/pdbsum/5r8e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5r8e ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/IL1B_HUMAN IL1B_HUMAN]] Produced by activated macrophages, IL-1 stimulates thymocyte proliferation by inducing IL-2 release, B-cell maturation and proliferation, and fibroblast growth factor activity. IL-1 proteins are involved in the inflammatory response, being identified as endogenous pyrogens, and are reported to stimulate the release of prostaglandin and collagenase from synovial cells.<ref>PMID:3920526</ref>	+	[https://www.uniprot.org/uniprot/IL1B_HUMAN IL1B_HUMAN] Produced by activated macrophages, IL-1 stimulates thymocyte proliferation by inducing IL-2 release, B-cell maturation and proliferation, and fibroblast growth factor activity. IL-1 proteins are involved in the inflammatory response, being identified as endogenous pyrogens, and are reported to stimulate the release of prostaglandin and collagenase from synovial cells.<ref>PMID:3920526</ref>
-	~~<div style="background-color:#fffaf0;">~~	+
-	~~== Publication Abstract from PubMed ==~~	+
-	Nowadays, it is possible to combine X-ray crystallography and fragment screening in a medium throughput fashion to chemically probe the surfaces used by proteins to interact and use the outcome of the screens to systematically design protein-protein inhibitors. To prove it, we first performed a bioinformatics analysis of the Protein Data Bank protein complexes, which revealed over 400 cases where the crystal lattice of the target in the free form is such that large portions of the interacting surfaces are free from lattice contacts and therefore accessible to fragments during soaks. Among the tractable complexes identified, we then performed single fragment crystal screens on two particular interesting cases: the Il1beta-ILR and p38alpha-TAB1 complexes. The result of the screens showed that fragments tend to bind in clusters, highlighting the small-molecule hotspots on the surface of the target protein. In most of the cases, the hotspots overlapped with the binding sites of the interacting proteins.	+
-		+
-	Mining the PDB for Tractable Cases Where X-ray Crystallography Combined with Fragment Screens Can Be Used to Systematically Design Protein-Protein Inhibitors: Two Test Cases Illustrated by IL1beta-IL1R and p38alpha-TAB1 Complexes.,Nichols C, Ng J, Keshu A, Kelly G, Conte MR, Marber MS, Fraternali F, De Nicola GF J Med Chem. 2020 Jul 1. doi: 10.1021/acs.jmedchem.0c00403. PMID:32543856<ref>PMID:32543856</ref>	+
-		+
-	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~	+
-	~~</div>~~	+
-	~~<div class="pdbe-citations 5r8e" style="background-color:#fffaf0;"></div~~>	+
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: ~~Nichols, C E]]~~	+	[[Category: De Nicola GF]]
-	~~[[Category:~~ Nicola~~, G F.De~~]]	+	[[Category: Nichols CE]]
-	[[Category: ~~Il-1 beta]]~~	+
-	~~[[Category: Pandda]]~~	+
-	~~[[Category: Sgc - diamond i04-1 fragment screening]]~~	+
-	~~[[Category: Signaling protein]]~~	+
-	~~[[Category: Xchemexplorer~~]]	+

OCA at 11:15, 22 July 2020

OCA — Wed, 22 Jul 2020 11:15:33 GMT

←Older revision		Revision as of 11:15, 22 July 2020
Line 1:		Line 1:

	==PanDDA analysis group deposition INTERLEUKIN-1 BETA -- Fragment Z57475877 in complex with INTERLEUKIN-1 BETA==		==PanDDA analysis group deposition INTERLEUKIN-1 BETA -- Fragment Z57475877 in complex with INTERLEUKIN-1 BETA==
-	<StructureSection load='5r8e' size='340' side='right'caption='[[5r8e]]' scene=''>	+	<StructureSection load='5r8e' size='340' side='right'caption='[[5r8e]], [[Resolution\|resolution]] 1.35Å' 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=5R8E OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5R8E FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5r8e]] 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=5R8E OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5R8E 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=5r8e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5r8e OCA], [http://pdbe.org/5r8e PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5r8e RCSB], [http://www.ebi.ac.uk/pdbsum/5r8e PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5r8e 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=S7S:~{N}-(2-ethyl-1,2,3,4-tetrazol-5-yl)butanamide'>S7S</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">IL1B, IL1F2 ([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'>[http://proteopedia.org/fgij/fg.htm?mol=5r8e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5r8e OCA], [http://pdbe.org/5r8e PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5r8e RCSB], [http://www.ebi.ac.uk/pdbsum/5r8e PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5r8e ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/IL1B_HUMAN IL1B_HUMAN]] Produced by activated macrophages, IL-1 stimulates thymocyte proliferation by inducing IL-2 release, B-cell maturation and proliferation, and fibroblast growth factor activity. IL-1 proteins are involved in the inflammatory response, being identified as endogenous pyrogens, and are reported to stimulate the release of prostaglandin and collagenase from synovial cells.<ref>PMID:3920526</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Nowadays, it is possible to combine X-ray crystallography and fragment screening in a medium throughput fashion to chemically probe the surfaces used by proteins to interact and use the outcome of the screens to systematically design protein-protein inhibitors. To prove it, we first performed a bioinformatics analysis of the Protein Data Bank protein complexes, which revealed over 400 cases where the crystal lattice of the target in the free form is such that large portions of the interacting surfaces are free from lattice contacts and therefore accessible to fragments during soaks. Among the tractable complexes identified, we then performed single fragment crystal screens on two particular interesting cases: the Il1beta-ILR and p38alpha-TAB1 complexes. The result of the screens showed that fragments tend to bind in clusters, highlighting the small-molecule hotspots on the surface of the target protein. In most of the cases, the hotspots overlapped with the binding sites of the interacting proteins.
		+
		+	Mining the PDB for Tractable Cases Where X-ray Crystallography Combined with Fragment Screens Can Be Used to Systematically Design Protein-Protein Inhibitors: Two Test Cases Illustrated by IL1beta-IL1R and p38alpha-TAB1 Complexes.,Nichols C, Ng J, Keshu A, Kelly G, Conte MR, Marber MS, Fraternali F, De Nicola GF J Med Chem. 2020 Jul 1. doi: 10.1021/acs.jmedchem.0c00403. PMID:32543856<ref>PMID:32543856</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 5r8e" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: De Nicola GF]]	+	[[Category: Nichols, C E]]
-	[[Category: ~~Nichols CE~~]]	+	[[Category: Nicola, G F.De]]
		+	[[Category: Il-1 beta]]
		+	[[Category: Pandda]]
		+	[[Category: Sgc - diamond i04-1 fragment screening]]
		+	[[Category: Signaling protein]]
		+	[[Category: Xchemexplorer]]

OCA at 05:37, 22 April 2020

OCA — Wed, 22 Apr 2020 05:37:57 GMT

←Older revision		Revision as of 05:37, 22 April 2020
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry 5r8e is ON HOLD~~	+	==PanDDA analysis group deposition INTERLEUKIN-1 BETA -- Fragment Z57475877 in complex with INTERLEUKIN-1 BETA==
-		+	<StructureSection load='5r8e' size='340' side='right'caption='[[5r8e]]' scene=''>
-	~~Authors: De Nicola, G.F., Nichols, C.E.~~	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5R8E OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5R8E FirstGlance]. <br>
-	~~Description:~~ PanDDA analysis group deposition INTERLEUKIN-1 BETA --Fragment Z57475877 in complex with INTERLEUKIN-1 BETA	+	</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=5r8e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5r8e OCA], [http://pdbe.org/5r8e PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5r8e RCSB], [http://www.ebi.ac.uk/pdbsum/5r8e PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5r8e ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	</table>
-	[[Category: De Nicola~~, G.F~~]]	+	__TOC__
-	[[Category: Nichols~~, C.E~~]]	+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: De Nicola GF]]
		+	[[Category: Nichols CE]]

OCA at 08:08, 27 March 2020

OCA — Fri, 27 Mar 2020 08:08:18 GMT

←Older revision		Revision as of 08:08, 27 March 2020
Line 3:		Line 3:
	The entry 5r8e is ON HOLD		The entry 5r8e is ON HOLD

-	Authors: ~~De_Nicola~~, G.F., Nichols, C.E.	+	Authors: De Nicola, G.F., Nichols, C.E.

	Description: PanDDA analysis group deposition INTERLEUKIN-1 BETA --Fragment Z57475877 in complex with INTERLEUKIN-1 BETA		Description: PanDDA analysis group deposition INTERLEUKIN-1 BETA --Fragment Z57475877 in complex with INTERLEUKIN-1 BETA
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
-	[[Category: ~~De_nicola~~, G.F]]	+	[[Category: De Nicola, G.F]]
	[[Category: Nichols, C.E]]		[[Category: Nichols, C.E]]

OCA: Protected "5r8e" [edit=sysop:move=sysop]

OCA — Wed, 11 Mar 2020 05:49:10 GMT

Protected "5r8e" [edit=sysop:move=sysop]

←Older revision

Revision as of 05:49, 11 March 2020

OCA: New page: '''Unreleased structure''' The entry 5r8e is ON HOLD Authors: De_Nicola, G.F., Nichols, C.E. Description: PanDDA analysis group deposition INTERLEUKIN-1 BETA --Fragment Z57475877 in co...

OCA — Wed, 11 Mar 2020 05:49:08 GMT

New page: '''Unreleased structure''' The entry 5r8e is ON HOLD Authors: De_Nicola, G.F., Nichols, C.E. Description: PanDDA analysis group deposition INTERLEUKIN-1 BETA --Fragment Z57475877 in co...

New page

'''Unreleased structure'''

The entry 5r8e is ON HOLD

Authors: De_Nicola, G.F., Nichols, C.E.

Description: PanDDA analysis group deposition INTERLEUKIN-1 BETA --Fragment Z57475877 in complex with INTERLEUKIN-1 BETA
[[Category: Unreleased Structures]]
[[Category: De_nicola, G.F]]
[[Category: Nichols, C.E]]