6qaw - Revision history

OCA at 07:41, 23 May 2019

OCA — Thu, 23 May 2019 07:41:27 GMT

←Older revision		Revision as of 07:41, 23 May 2019
Line 3:		Line 3:
	<StructureSection load='6qaw' size='340' side='right'caption='[[6qaw]], [[Resolution\|resolution]] 1.84Å' scene=''>		<StructureSection load='6qaw' size='340' side='right'caption='[[6qaw]], [[Resolution\|resolution]] 1.84Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6qaw]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6QAW OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6QAW FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6qaw]] 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=6QAW OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6QAW FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=HVE:[1-(7~{H}-pyrrolo[2,3-d]pyrimidin-4-yl)piperidin-4-yl]methylazanium'>HVE</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=HVE:[1-(7~{H}-pyrrolo[2,3-d]pyrimidin-4-yl)piperidin-4-yl]methylazanium'>HVE</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
	<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CME:S,S-(2-HYDROXYETHYL)THIOCYSTEINE'>CME</scene></td></tr>		<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CME:S,S-(2-HYDROXYETHYL)THIOCYSTEINE'>CME</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">MAPK1, ERK2, PRKM1, PRKM2 ([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/Mitogen-activated_protein_kinase Mitogen-activated protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.24 2.7.11.24] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Mitogen-activated_protein_kinase Mitogen-activated protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.24 2.7.11.24] </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=6qaw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6qaw OCA], [http://pdbe.org/6qaw PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6qaw RCSB], [http://www.ebi.ac.uk/pdbsum/6qaw PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6qaw 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=6qaw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6qaw OCA], [http://pdbe.org/6qaw PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6qaw RCSB], [http://www.ebi.ac.uk/pdbsum/6qaw PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6qaw ProSAT]</span></td></tr>
Line 24:		Line 25:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Mitogen-activated protein kinase]]		[[Category: Mitogen-activated protein kinase]]

OCA at 06:47, 27 March 2019

OCA — Wed, 27 Mar 2019 06:47:59 GMT

←Older revision		Revision as of 06:47, 27 March 2019
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6qaw is ~~ON HOLD~~	+	==ERK2 mini-fragment binding==
		+	<StructureSection load='6qaw' size='340' side='right'caption='[[6qaw]], [[Resolution\|resolution]] 1.84Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[6qaw]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6QAW OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6QAW FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=HVE:[1-(7~{H}-pyrrolo[2,3-d]pyrimidin-4-yl)piperidin-4-yl]methylazanium'>HVE</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
		+	<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CME:S,S-(2-HYDROXYETHYL)THIOCYSTEINE'>CME</scene></td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Mitogen-activated_protein_kinase Mitogen-activated protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.24 2.7.11.24] </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=6qaw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6qaw OCA], [http://pdbe.org/6qaw PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6qaw RCSB], [http://www.ebi.ac.uk/pdbsum/6qaw PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6qaw ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/MK01_HUMAN MK01_HUMAN]] Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK1/ERK2 and MAPK3/ERK1 are the 2 MAPKs which play an important role in the MAPK/ERK cascade. They participate also in a signaling cascade initiated by activated KIT and KITLG/SCF. Depending on the cellular context, the MAPK/ERK cascade mediates diverse biological functions such as cell growth, adhesion, survival and differentiation through the regulation of transcription, translation, cytoskeletal rearrangements. The MAPK/ERK cascade plays also a role in initiation and regulation of meiosis, mitosis, and postmitotic functions in differentiated cells by phosphorylating a number of transcription factors. About 160 substrates have already been discovered for ERKs. Many of these substrates are localized in the nucleus, and seem to participate in the regulation of transcription upon stimulation. However, other substrates are found in the cytosol as well as in other cellular organelles, and those are responsible for processes such as translation, mitosis and apoptosis. Moreover, the MAPK/ERK cascade is also involved in the regulation of the endosomal dynamics, including lysosome processing and endosome cycling through the perinuclear recycling compartment (PNRC); as well as in the fragmentation of the Golgi apparatus during mitosis. The substrates include transcription factors (such as ATF2, BCL6, ELK1, ERF, FOS, HSF4 or SPZ1), cytoskeletal elements (such as CANX, CTTN, GJA1, MAP2, MAPT, PXN, SORBS3 or STMN1), regulators of apoptosis (such as BAD, BTG2, CASP9, DAPK1, IER3, MCL1 or PPARG), regulators of translation (such as EIF4EBP1) and a variety of other signaling-related molecules (like ARHGEF2, DCC, FRS2 or GRB10). Protein kinases (such as RAF1, RPS6KA1/RSK1, RPS6KA3/RSK2, RPS6KA2/RSK3, RPS6KA6/RSK4, SYK, MKNK1/MNK1, MKNK2/MNK2, RPS6KA5/MSK1, RPS6KA4/MSK2, MAPKAPK3 or MAPKAPK5) and phosphatases (such as DUSP1, DUSP4, DUSP6 or DUSP16) are other substrates which enable the propagation the MAPK/ERK signal to additional cytosolic and nuclear targets, thereby extending the specificity of the cascade. May play a role in the spindle assembly checkpoint.<ref>PMID:7588608</ref> <ref>PMID:8622688</ref> <ref>PMID:9480836</ref> <ref>PMID:9687510</ref> <ref>PMID:9649500</ref> <ref>PMID:9596579</ref> <ref>PMID:10637505</ref> <ref>PMID:10617468</ref> <ref>PMID:11154262</ref> <ref>PMID:12110590</ref> <ref>PMID:12356731</ref> <ref>PMID:12974390</ref> <ref>PMID:12794087</ref> <ref>PMID:12792650</ref> <ref>PMID:15184391</ref> <ref>PMID:15241487</ref> <ref>PMID:15952796</ref> <ref>PMID:15616583</ref> <ref>PMID:15788397</ref> <ref>PMID:15664191</ref> <ref>PMID:16581800</ref> <ref>PMID:19879846</ref> <ref>PMID:19265199</ref> Acts as a transcriptional repressor. Binds to a [GC]AAA[GC] consensus sequence. Repress the expression of interferon gamma-induced genes. Seems to bind to the promoter of CCL5, DMP1, IFIH1, IFITM1, IRF7, IRF9, LAMP3, OAS1, OAS2, OAS3 and STAT1. Transcriptional activity is independent of kinase activity.<ref>PMID:7588608</ref> <ref>PMID:8622688</ref> <ref>PMID:9480836</ref> <ref>PMID:9687510</ref> <ref>PMID:9649500</ref> <ref>PMID:9596579</ref> <ref>PMID:10637505</ref> <ref>PMID:10617468</ref> <ref>PMID:11154262</ref> <ref>PMID:12110590</ref> <ref>PMID:12356731</ref> <ref>PMID:12974390</ref> <ref>PMID:12794087</ref> <ref>PMID:12792650</ref> <ref>PMID:15184391</ref> <ref>PMID:15241487</ref> <ref>PMID:15952796</ref> <ref>PMID:15616583</ref> <ref>PMID:15788397</ref> <ref>PMID:15664191</ref> <ref>PMID:16581800</ref> <ref>PMID:19879846</ref> <ref>PMID:19265199</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	We present a novel crystallographic screening methodology (MiniFrags) that employs high-concentration aqueous soaks with a chemically diverse and ultra-low-molecular-weight library (heavy atom count 5-7) to identify ligand-binding hot and warm spots on proteins. We propose that MiniFrag screening represents a highly effective method for guiding optimisation of fragment-derived lead compounds or chemical tools and that the high screening hit rates reflect enhanced sampling of chemical space.

-	~~Authors:~~ O'Reilly, M., Cleasby, A., Davies~~, T.G.~~, Hall~~, R.~~, Ludlow~~, F.~~, Murray~~, C.W.~~, Tisi, D., Jhoti, H.	+	Crystallographic screening using ultra-low-molecular-weight ligands to guide drug design.,O'Reilly M, Cleasby A, Davies TG, Hall RJ, Ludlow RF, Murray CW, Tisi D, Jhoti H Drug Discov Today. 2019 Mar 14. pii: S1359-6446(19)30001-7. doi:, 10.1016/j.drudis.2019.03.009. PMID:30878562<ref>PMID:30878562</ref>

-	~~Description: ERK2 mini~~-~~fragment binding~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased~~ Structures]]	+	</div>
-	[[Category: ~~Tisi, D]]~~	+	<div class="pdbe-citations 6qaw" style="background-color:#fffaf0;"></div>
-	~~[[Category: Davies, T.G~~]]	+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Mitogen-activated protein kinase]]
	[[Category: Cleasby, A]]		[[Category: Cleasby, A]]
		+	[[Category: Davies, T G]]
		+	[[Category: Hall, R]]
	[[Category: Jhoti, H]]		[[Category: Jhoti, H]]
-	[[Category: O'Reilly, M]]
	[[Category: Ludlow, F]]		[[Category: Ludlow, F]]
-	[[Category: ~~Hall~~, R]]	+	[[Category: Murray, C W]]
-	[[Category: ~~Murray~~, ~~C.W~~]]	+	[[Category: Reilly, M O]]
		+	[[Category: Tisi, D]]
		+	[[Category: Atp binding]]
		+	[[Category: Ser/thr kinase]]
		+	[[Category: Signal transduction]]
		+	[[Category: Signaling protein]]

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

OCA — Wed, 26 Dec 2018 07:04:01 GMT

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

←Older revision

Revision as of 07:04, 26 December 2018

OCA: New page: '''Unreleased structure''' The entry 6qaw is ON HOLD Authors: O'Reilly, M., Cleasby, A., Davies, T.G., Hall, R., Ludlow, F., Murray, C.W., Tisi, D., Jhoti, H. Description: ERK2 mini-fr...

OCA — Wed, 26 Dec 2018 07:04:00 GMT

New page: '''Unreleased structure''' The entry 6qaw is ON HOLD Authors: O'Reilly, M., Cleasby, A., Davies, T.G., Hall, R., Ludlow, F., Murray, C.W., Tisi, D., Jhoti, H. Description: ERK2 mini-fr...

New page

'''Unreleased structure'''

The entry 6qaw is ON HOLD

Authors: O'Reilly, M., Cleasby, A., Davies, T.G., Hall, R., Ludlow, F., Murray, C.W., Tisi, D., Jhoti, H.

Description: ERK2 mini-fragment binding
[[Category: Unreleased Structures]]
[[Category: Tisi, D]]
[[Category: Davies, T.G]]
[[Category: Cleasby, A]]
[[Category: Jhoti, H]]
[[Category: O'Reilly, M]]
[[Category: Ludlow, F]]
[[Category: Hall, R]]
[[Category: Murray, C.W]]