8atn - Revision history

OCA at 06:18, 6 September 2023

OCA — Wed, 06 Sep 2023 06:18:09 GMT

←Older revision		Revision as of 06:18, 6 September 2023
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 8atn ~~is ON HOLD until Paper Publication~~	+	==Discovery of IRAK4 Inhibitor 38==
-		+	<StructureSection load='8atn' size='340' side='right'caption='[[8atn]], [[Resolution\|resolution]] 2.17Å' scene=''>
-	~~Authors~~: ~~Schafer, M~~.~~, Bothe, U~~.~~, Schmidt, N~~.~~, Gunther, J~~.~~, Nubbemeyer, R~~.~~, Siebeneicher, H~~.~~, Ring, S~~.~~, Boemer, U~~.~~, Peters, M~~., ~~Denner, K~~., ~~Himmel~~, H., ~~Sutter, A~~., ~~Terebesi, I~~., ~~Lange, M~~., ~~Wenger, A~~.M., ~~Guimond, N~~., ~~Thaler~~, T., ~~Platzek, J~~., ~~Eberspaecher, U~~., ~~Steuber, H~~., ~~Steinmeyer, A~~., ~~Zollner, T~~.M.	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[8atn]] 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=8ATN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8ATN FirstGlance]. <br>
-	~~Description~~: ~~Discovery of IRAK4 Inhibitor 38~~	+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 2.171Å</td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=O06:~{N}-[3-methyl-2-(3-methyl-3-oxidanyl-butyl)-6-(2-oxidanylpropan-2-yl)benzimidazol-5-yl]-6-(trifluoromethyl)pyridine-2-carboxamide'>O06</scene>, <scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene>, <scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></td></tr>
-	[[Category: ~~Lange, M~~]]	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8atn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8atn OCA], [https://pdbe.org/8atn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8atn RCSB], [https://www.ebi.ac.uk/pdbsum/8atn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8atn ProSAT]</span></td></tr>
-	[[Category: ~~Gunther, J~~]]	+	</table>
-	[[Category: ~~Guimond, N~~]]	+	== Disease ==
-	[[Category: ~~Steinmeyer, A~~]]	+	[https://www.uniprot.org/uniprot/IRAK4_HUMAN IRAK4_HUMAN] Defects in IRAK4 are the cause of recurrent isolated invasive pneumococcal disease type 1 (IPD1) [MIM:[https://omim.org/entry/610799 610799]. Recurrent invasive pneumococcal disease (IPD) is defined as two episodes of IPD occurring at least 1 month apart, whether caused by the same or different serotypes or strains. Recurrent IPD occurs in at least 2% of patients in most series, making IPD the most important known risk factor for subsequent IPD.<ref>PMID:16950813</ref> Defects in IRAK4 are the cause of IRAK4 deficiency (IRAK4D) [MIM:[https://omim.org/entry/607676 607676]. IRAK4 deficiency causes extracellular pyogenic bacterial and fungal infections in otherwise healthy children.<ref>PMID:12925671</ref> <ref>PMID:12637671</ref>
-	[[Category: ~~Terebesi, I~~]]	+	== Function ==
-	[[Category: ~~Denner, K~~]]	+	[https://www.uniprot.org/uniprot/IRAK4_HUMAN IRAK4_HUMAN] Serine/threonine-protein kinase that plays a critical role in initiating innate immune response against foreign pathogens. Involved in Toll-like receptor (TLR) and IL-1R signaling pathways. Is rapidly recruited by MYD88 to the receptor-signaling complex upon TLR activation to form the Myddosome together with IRAK2. Phosphorylates initially IRAK1, thus stimulating the kinase activity and intensive autophosphorylation of IRAK1. Phosphorylates E3 ubiquitin ligases Pellino proteins (PELI1, PELI2 and PELI3) to promote pellino-mediated polyubiquitination of IRAK1. Then, the ubiquitin-binding domain of IKBKG/NEMO binds to polyubiquitinated IRAK1 bringing together the IRAK1-MAP3K7/TAK1-TRAF6 complex and the NEMO-IKKA-IKKB complex. In turn, MAP3K7/TAK1 activates IKKs (CHUK/IKKA and IKBKB/IKKB) leading to NF-kappa-B nuclear translocation and activation. Alternatively, phosphorylates TIRAP to promote its ubiquitination and subsequent degradation. Phosphorylates NCF1 and regulates NADPH oxidase activation after LPS stimulation suggesting a similar mechanism during microbial infections.<ref>PMID:11960013</ref> <ref>PMID:12538665</ref> <ref>PMID:15084582</ref> <ref>PMID:17217339</ref> <ref>PMID:17337443</ref> <ref>PMID:17997719</ref> <ref>PMID:20400509</ref>
-	[[Category: ~~Peters, M~~]]	+	== References ==
-	[[Category: ~~Thaler, T~~]]	+	<references/>
-	[[Category: ~~Sutter, A~~]]	+	__TOC__
-	[[Category: ~~Schafer,~~ M]]	+	</StructureSection>
-	[[Category: ~~Zollner, T.M~~]]	+	[[Category: Homo sapiens]]
-	[[Category: ~~Bothe, U~~]]	+	[[Category: Large Structures]]
-	[[Category: ~~Platzek, J~~]]	+	[[Category: Boemer U]]
-	[[Category: ~~Ring, S~~]]	+	[[Category: Bothe U]]
-	[[Category: ~~Eberspaecher, U~~]]	+	[[Category: Denner K]]
-	[[Category: ~~Wenger,~~ A.M]]	+	[[Category: Eberspaecher U]]
-	[[Category: Steuber, H]]	+	[[Category: Guimond N]]
-	[[Category: ~~Schmidt, N~~]]	+	[[Category: Gunther J]]
-	[[Category: ~~Himmel, H~~]]	+	[[Category: Himmel H]]
-	[[Category: ~~Siebeneicher, H~~]]	+	[[Category: Lange M]]
-	[[Category: ~~Boemer, U~~]]	+	[[Category: Nubbemeyer R]]
-	[[Category: ~~Nubbemeyer, R~~]]	+	[[Category: Peters M]]
		+	[[Category: Platzek J]]
		+	[[Category: Ring S]]
		+	[[Category: Schafer M]]
		+	[[Category: Schmidt N]]
		+	[[Category: Siebeneicher H]]
		+	[[Category: Steinmeyer A]]
		+	[[Category: Steuber H]]
		+	[[Category: Sutter A]]
		+	[[Category: Terebesi I]]
		+	[[Category: Thaler T]]
		+	[[Category: Wenger AM]]
		+	[[Category: Zollner TM]]

OCA at 07:12, 14 December 2022

OCA — Wed, 14 Dec 2022 07:12:02 GMT

←Older revision		Revision as of 07:12, 14 December 2022
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	Authors: Schafer, M., Bothe, U., Schmidt, N., Gunther, J., Nubbemeyer, R., Siebeneicher, H., Ring, S., Boemer, U., Peters, M., Denner, K., Himmel, H., Sutter, A., Terebesi, I., Lange, M., Wenger, A.M., Guimond, N., Thaler, T., Platzek, J., Eberspaecher, U., Steuber, H., Steinmeyer, A., Zollner, T.M.		Authors: Schafer, M., Bothe, U., Schmidt, N., Gunther, J., Nubbemeyer, R., Siebeneicher, H., Ring, S., Boemer, U., Peters, M., Denner, K., Himmel, H., Sutter, A., Terebesi, I., Lange, M., Wenger, A.M., Guimond, N., Thaler, T., Platzek, J., Eberspaecher, U., Steuber, H., Steinmeyer, A., Zollner, T.M.

-	Description: Discovery of IRAK4 ~~Inhibitors BAY1834845 and BAY1830839~~	+	Description: Discovery of IRAK4 Inhibitor 38
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
	[[Category: Lange, M]]		[[Category: Lange, M]]

OCA at 04:31, 28 September 2022

OCA — Wed, 28 Sep 2022 04:31:36 GMT

←Older revision		Revision as of 04:31, 28 September 2022
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 8atn is ON HOLD	+	The entry 8atn is ON HOLD until Paper Publication

	Authors: Schafer, M., Bothe, U., Schmidt, N., Gunther, J., Nubbemeyer, R., Siebeneicher, H., Ring, S., Boemer, U., Peters, M., Denner, K., Himmel, H., Sutter, A., Terebesi, I., Lange, M., Wenger, A.M., Guimond, N., Thaler, T., Platzek, J., Eberspaecher, U., Steuber, H., Steinmeyer, A., Zollner, T.M.		Authors: Schafer, M., Bothe, U., Schmidt, N., Gunther, J., Nubbemeyer, R., Siebeneicher, H., Ring, S., Boemer, U., Peters, M., Denner, K., Himmel, H., Sutter, A., Terebesi, I., Lange, M., Wenger, A.M., Guimond, N., Thaler, T., Platzek, J., Eberspaecher, U., Steuber, H., Steinmeyer, A., Zollner, T.M.

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

OCA — Wed, 31 Aug 2022 05:28:12 GMT

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

←Older revision

Revision as of 05:28, 31 August 2022

OCA: New page: '''Unreleased structure''' The entry 8atn is ON HOLD Authors: Schafer, M., Bothe, U., Schmidt, N., Gunther, J., Nubbemeyer, R., Siebeneicher, H., Ring, S., Boemer, U., Peters, M., Denne...

OCA — Wed, 31 Aug 2022 05:28:11 GMT

New page: '''Unreleased structure''' The entry 8atn is ON HOLD Authors: Schafer, M., Bothe, U., Schmidt, N., Gunther, J., Nubbemeyer, R., Siebeneicher, H., Ring, S., Boemer, U., Peters, M., Denne...

New page

'''Unreleased structure'''

The entry 8atn is ON HOLD

Authors: Schafer, M., Bothe, U., Schmidt, N., Gunther, J., Nubbemeyer, R., Siebeneicher, H., Ring, S., Boemer, U., Peters, M., Denner, K., Himmel, H., Sutter, A., Terebesi, I., Lange, M., Wenger, A.M., Guimond, N., Thaler, T., Platzek, J., Eberspaecher, U., Steuber, H., Steinmeyer, A., Zollner, T.M.

Description: Discovery of IRAK4 Inhibitors BAY1834845 and BAY1830839
[[Category: Unreleased Structures]]
[[Category: Lange, M]]
[[Category: Gunther, J]]
[[Category: Guimond, N]]
[[Category: Steinmeyer, A]]
[[Category: Terebesi, I]]
[[Category: Denner, K]]
[[Category: Peters, M]]
[[Category: Thaler, T]]
[[Category: Sutter, A]]
[[Category: Schafer, M]]
[[Category: Zollner, T.M]]
[[Category: Bothe, U]]
[[Category: Platzek, J]]
[[Category: Ring, S]]
[[Category: Eberspaecher, U]]
[[Category: Wenger, A.M]]
[[Category: Steuber, H]]
[[Category: Schmidt, N]]
[[Category: Himmel, H]]
[[Category: Siebeneicher, H]]
[[Category: Boemer, U]]
[[Category: Nubbemeyer, R]]