7t1k - Revision history

OCA at 16:57, 18 October 2023

OCA — Wed, 18 Oct 2023 16:57:48 GMT

←Older revision		Revision as of 16:57, 18 October 2023
Line 1:		Line 1:

	==Crystal structure of a superbinder Fes SH2 domain (sFes1) in complex with a high affinity phosphopeptide==		==Crystal structure of a superbinder Fes SH2 domain (sFes1) in complex with a high affinity phosphopeptide==
-	<StructureSection load='7t1k' size='340' side='right'caption='[[7t1k]]' scene=''>	+	<StructureSection load='7t1k' size='340' side='right'caption='[[7t1k]], [[Resolution\|resolution]] 1.25Å' 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=7T1K OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7T1K FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7t1k]] 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=7T1K OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7T1K FirstGlance]. <br>
-	</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=7t1k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7t1k OCA], [https://pdbe.org/7t1k PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7t1k RCSB], [https://www.ebi.ac.uk/pdbsum/7t1k PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7t1k ProSAT]</span></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]] 1.25Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=MLI:MALONATE+ION'>MLI</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</scene></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=7t1k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7t1k OCA], [https://pdbe.org/7t1k PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7t1k RCSB], [https://www.ebi.ac.uk/pdbsum/7t1k PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7t1k ProSAT]</span></td></tr>
	</table>		</table>
		+	== Disease ==
		+	[https://www.uniprot.org/uniprot/FES_HUMAN FES_HUMAN] Note=Has been shown to act as proto-oncogene in some types of cancer, possibly due to abnormal activation of the kinase. Has been shown to act as tumor suppressor in other types of cancer. Expressed and present as activated kinase in a subset of acute myeloid leukemia patients; promotes survival of leukemia cells (PubMed:20111072). Expression is absent in K562 leukemia cells; ectopic expression of FSP/FES restores myeloid differentiation (PubMed:2656706). May function as tumor suppressor in colorectal cancer; expression is reduced or absent in samples from some colon cancer patients (PubMed:16455651). Ectopic expression of FSP/FES suppresses anchorage-independent growth in colon cancer cell lines (PubMed:16455651). Up-regulated in prostate cancer, and might be a predictor of recurrence after radical surgery (PubMed:21563194). May promote growth of renal carcinoma cells (PubMed:19082481).
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/FES_HUMAN FES_HUMAN] Tyrosine-protein kinase that acts downstream of cell surface receptors and plays a role in the regulation of the actin cytoskeleton, microtubule assembly, cell attachment and cell spreading. Plays a role in FCER1 (high affinity immunoglobulin epsilon receptor)-mediated signaling in mast cells. Acts down-stream of the activated FCER1 receptor and the mast/stem cell growth factor receptor KIT. Plays a role in the regulation of mast cell degranulation. Plays a role in the regulation of cell differentiation and promotes neurite outgrowth in response to NGF signaling. Plays a role in cell scattering and cell migration in response to HGF-induced activation of EZR. Phosphorylates BCR and down-regulates BCR kinase activity. Phosphorylates HCLS1/HS1, PECAM1, STAT3 and TRIM28.<ref>PMID:2656706</ref> <ref>PMID:8955135</ref> <ref>PMID:11509660</ref> <ref>PMID:15302586</ref> <ref>PMID:15485904</ref> <ref>PMID:16455651</ref> <ref>PMID:17595334</ref> <ref>PMID:18046454</ref> <ref>PMID:19051325</ref> <ref>PMID:19082481</ref> <ref>PMID:19001085</ref> <ref>PMID:20111072</ref> <ref>PMID:21563194</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	A comprehensive analysis of the phosphoproteome is essential for understanding molecular mechanisms of human diseases. However, current tools used to enrich phosphotyrosine (pTyr) are limited in their applicability and scope. Here, we engineered new superbinder Src-Homology 2 (SH2) domains that enrich diverse sets of pTyr-peptides. We used phage display to select a Fes-SH2 domain variant (superFes; sFes(1)) with high affinity for pTyr and solved its structure bound to a pTyr-peptide. We performed systematic structure-function analyses of the superbinding mechanisms of sFes(1) and superSrc-SH2 (sSrc(1)), another SH2 superbinder. We grafted the superbinder motifs from sFes(1) and sSrc(1) into 17 additional SH2 domains and confirmed increased binding affinity for specific pTyr-peptides. Using mass spectrometry (MS), we demonstrated that SH2 superbinders have distinct specificity profiles and superior capabilities to enrich pTyr-peptides. Finally, using combinations of SH2 superbinders as affinity purification (AP) tools we showed that unique subsets of pTyr-peptides can be enriched with unparalleled depth and coverage.
		+
		+	Engineered SH2 Domains for Targeted Phosphoproteomics.,Martyn GD, Veggiani G, Kusebauch U, Morrone SR, Yates BP, Singer AU, Tong J, Manczyk N, Gish G, Sun Z, Kurinov I, Sicheri F, Moran MF, Moritz RL, Sidhu SS ACS Chem Biol. 2022 Jun 17;17(6):1472-1484. doi: 10.1021/acschembio.2c00051. Epub, 2022 May 25. PMID:35613471<ref>PMID:35613471</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7t1k" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Kurinov I]]		[[Category: Kurinov I]]

OCA at 10:08, 31 August 2022

OCA — Wed, 31 Aug 2022 10:08:10 GMT

←Older revision		Revision as of 10:08, 31 August 2022
Line 1:		Line 1:

-	====	+	==Crystal structure of a superbinder Fes SH2 domain (sFes1) in complex with a high affinity phosphopeptide==
	<StructureSection load='7t1k' size='340' side='right'caption='[[7t1k]]' scene=''>		<StructureSection load='7t1k' size='340' side='right'caption='[[7t1k]]' 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= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br>	+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7T1K OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7T1K FirstGlance]. <br>
	</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=7t1k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7t1k OCA], [https://pdbe.org/7t1k PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7t1k RCSB], [https://www.ebi.ac.uk/pdbsum/7t1k PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7t1k ProSAT]</span></td></tr>		</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=7t1k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7t1k OCA], [https://pdbe.org/7t1k PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7t1k RCSB], [https://www.ebi.ac.uk/pdbsum/7t1k PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7t1k ProSAT]</span></td></tr>
	</table>		</table>
Line 9:		Line 9:
	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: ~~Z-disk~~]]	+	[[Category: Kurinov I]]
		+	[[Category: Martyn GD]]
		+	[[Category: Sicheri F]]
		+	[[Category: Sidhu SS]]
		+	[[Category: Singer AU]]
		+	[[Category: Veggiani G]]

OCA at 04:49, 25 August 2022

OCA — Thu, 25 Aug 2022 04:49:17 GMT

←Older revision		Revision as of 04:49, 25 August 2022
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 7t1k ~~is ON HOLD until Paper Publication~~	+	====
-		+	<StructureSection load='7t1k' size='340' side='right'caption='[[7t1k]]' scene=''>
-	~~Authors~~:	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br>
-	~~Description~~:	+	</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=7t1k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7t1k OCA], [https://pdbe.org/7t1k PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7t1k RCSB], [https://www.ebi.ac.uk/pdbsum/7t1k PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7t1k ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	</table>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Z-disk]]

OCA at 05:25, 27 January 2022

OCA — Thu, 27 Jan 2022 05:25:56 GMT

←Older revision		Revision as of 05:25, 27 January 2022
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 7t1k is ON HOLD	+	The entry 7t1k is ON HOLD until Paper Publication

	Authors:		Authors:

OCA: Protected "7t1k" [edit=sysop:move=sysop]

OCA — Wed, 08 Dec 2021 08:39:15 GMT

Protected "7t1k" [edit=sysop:move=sysop]

←Older revision

Revision as of 08:39, 8 December 2021

OCA: New page: '''Unreleased structure''' The entry 7t1k is ON HOLD Authors: Description: Category: Unreleased Structures

OCA — Wed, 08 Dec 2021 08:39:14 GMT

New page: '''Unreleased structure''' The entry 7t1k is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 7t1k is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]