6n7b - Revision history

OCA at 08:21, 21 May 2019

OCA — Tue, 21 May 2019 08:21:00 GMT

←Older revision		Revision as of 08:21, 21 May 2019
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	<StructureSection load='6n7b' size='340' side='right'caption='[[6n7b]], [[Resolution\|resolution]] 1.81Å' scene=''>		<StructureSection load='6n7b' size='340' side='right'caption='[[6n7b]], [[Resolution\|resolution]] 1.81Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6n7b]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6N7B OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6N7B FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6n7b]] 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=6N7B OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6N7B FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=KEY:N-[3-(5-chloro-2-methoxyphenyl)-1-methyl-1H-pyrazol-4-yl]-1H-pyrazolo[4,3-c]pyridine-7-carboxamide'>KEY</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=KEY:N-[3-(5-chloro-2-methoxyphenyl)-1-methyl-1H-pyrazol-4-yl]-1H-pyrazolo[4,3-c]pyridine-7-carboxamide'>KEY</scene></td></tr>
	<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</scene></td></tr>		<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">JAK1, JAK1A, JAK1B ([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/Non-specific_protein-tyrosine_kinase Non-specific protein-tyrosine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.2 2.7.10.2] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_protein-tyrosine_kinase Non-specific protein-tyrosine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.2 2.7.10.2] </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=6n7b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6n7b OCA], [http://pdbe.org/6n7b PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6n7b RCSB], [http://www.ebi.ac.uk/pdbsum/6n7b PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6n7b 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=6n7b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6n7b OCA], [http://pdbe.org/6n7b PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6n7b RCSB], [http://www.ebi.ac.uk/pdbsum/6n7b PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6n7b ProSAT]</span></td></tr>
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Non-specific protein-tyrosine kinase]]		[[Category: Non-specific protein-tyrosine kinase]]

OCA at 07:00, 24 April 2019

OCA — Wed, 24 Apr 2019 07:00:15 GMT

←Older revision		Revision as of 07:00, 24 April 2019
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-	'''Unreleased structure'''

-	~~The entry~~ 6n7b is ~~ON HOLD until Paper~~ Publication	+	==Structure of the human JAK1 kinase domain with compound 38==
		+	<StructureSection load='6n7b' size='340' side='right'caption='[[6n7b]], [[Resolution\|resolution]] 1.81Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[6n7b]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6N7B OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6N7B FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=KEY:N-[3-(5-chloro-2-methoxyphenyl)-1-methyl-1H-pyrazol-4-yl]-1H-pyrazolo[4,3-c]pyridine-7-carboxamide'>KEY</scene></td></tr>
		+	<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</scene></td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_protein-tyrosine_kinase Non-specific protein-tyrosine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.2 2.7.10.2] </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=6n7b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6n7b OCA], [http://pdbe.org/6n7b PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6n7b RCSB], [http://www.ebi.ac.uk/pdbsum/6n7b PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6n7b ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/JAK1_HUMAN JAK1_HUMAN]] Tyrosine kinase of the non-receptor type, involved in the IFN-alpha/beta/gamma signal pathway. Kinase partner for the interleukin (IL)-2 receptor.
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Disruption of interleukin-13 (IL-13) signaling with large molecule antibody therapies has shown promise in diseases of allergic inflammation. Given that IL-13 recruits several members of the Janus Kinase family (JAK1, JAK2, and TYK2) to its receptor complex, JAK inhibition may offer an alternate small molecule approach to disrupting IL-13 signaling. Herein we demonstrate that JAK1 is likely the isoform most important to IL-13 signaling. Structure-based design was then used to improve the JAK1 potency of a series of previously reported JAK2 inhibitors. The ability to impede IL-13 signaling was thereby significantly improved, with the best compounds exhibiting single digit nM IC50's in cell-based assays dependent upon IL-13 signaling. Appropriate substitution was further found to influence inhibition of a key off-target, LRRK2. Finally, the most potent compounds were found to be metabolically labile, which makes them ideal scaffolds for further development as topical agents for IL-13 mediated diseases of the lungs and skin (for example asthma and atopic dermatitis, respectively).

-	~~Authors:~~ Lupardus, P.J., ~~Brown, D~~.	+	Discovery of a class of highly potent Janus Kinase 1/2 (JAK1/2) inhibitors demonstrating effective cell-based blockade of IL-13 signaling.,Zak M, Hanan EJ, Lupardus P, Brown DG, Robinson C, Siu M, Lyssikatos JP, Romero FA, Zhao G, Kellar T, Mendonca R, Ray NC, Goodacre SC, Crackett PH, McLean N, Hurley CA, Yuen PW, Cheng YX, Liu X, Liimatta M, Kohli PB, Nonomiya J, Salmon G, Buckley G, Lloyd J, Gibbons P, Ghilardi N, Kenny JR, Johnson A Bioorg Med Chem Lett. 2019 Apr 4. pii: S0960-894X(19)30217-3. doi:, 10.1016/j.bmcl.2019.04.008. PMID:30981576<ref>PMID:30981576</ref>

-	~~Description: Structure~~ of the ~~human JAK1 kinase domain with compound 38~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased~~ Structures]]	+	</div>
		+	<div class="pdbe-citations 6n7b" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Non-specific protein-tyrosine kinase]]
	[[Category: Brown, D]]		[[Category: Brown, D]]
-	[[Category: Lupardus, P.J]]	+	[[Category: Lupardus, P J]]
		+	[[Category: Il-13]]
		+	[[Category: Il13]]
		+	[[Category: Immune system]]
		+	[[Category: Jak1]]
		+	[[Category: Jak2]]
		+	[[Category: Jak3]]
		+	[[Category: Tyk2]]

OCA at 06:27, 30 January 2019

OCA — Wed, 30 Jan 2019 06:27:00 GMT

←Older revision		Revision as of 06:27, 30 January 2019
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6n7b is ON HOLD	+	The entry 6n7b is ON HOLD until Paper Publication

	Authors: Lupardus, P.J., Brown, D.		Authors: Lupardus, P.J., Brown, D.
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	Description: Structure of the human JAK1 kinase domain with compound 38		Description: Structure of the human JAK1 kinase domain with compound 38
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
-	[[Category: Lupardus, P.J]]
	[[Category: Brown, D]]		[[Category: Brown, D]]
		+	[[Category: Lupardus, P.J]]

OCA: Protected "6n7b" [edit=sysop:move=sysop]

OCA — Wed, 05 Dec 2018 05:18:46 GMT

Protected "6n7b" [edit=sysop:move=sysop]

←Older revision

Revision as of 05:18, 5 December 2018

OCA: New page: '''Unreleased structure''' The entry 6n7b is ON HOLD Authors: Lupardus, P.J., Brown, D. Description: Structure of the human JAK1 kinase domain with compound 38 [[Category: Unreleased S...

OCA — Wed, 05 Dec 2018 05:18:45 GMT

New page: '''Unreleased structure''' The entry 6n7b is ON HOLD Authors: Lupardus, P.J., Brown, D. Description: Structure of the human JAK1 kinase domain with compound 38 [[Category: Unreleased S...

New page

'''Unreleased structure'''

The entry 6n7b is ON HOLD

Authors: Lupardus, P.J., Brown, D.

Description: Structure of the human JAK1 kinase domain with compound 38
[[Category: Unreleased Structures]]
[[Category: Lupardus, P.J]]
[[Category: Brown, D]]