5wpm - Revision history

OCA at 06:58, 14 March 2018

2018-03-14T06:58:04Z

←Older revision		Revision as of 06:58, 14 March 2018
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	<StructureSection load='5wpm' size='340' side='right' caption='[[5wpm]], [[Resolution\|resolution]] 1.72Å' scene=''>		<StructureSection load='5wpm' size='340' side='right' caption='[[5wpm]], [[Resolution\|resolution]] 1.72Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5wpm]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5WPM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5WPM FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5wpm]] is a 3 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=5WPM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5WPM FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GNP:PHOSPHOAMINOPHOSPHONIC+ACID-GUANYLATE+ESTER'>GNP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=GNP:PHOSPHOAMINOPHOSPHONIC+ACID-GUANYLATE+ESTER'>GNP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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">KRAS, KRAS2, RASK2 ([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://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5wpm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5wpm OCA], [http://pdbe.org/5wpm PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5wpm RCSB], [http://www.ebi.ac.uk/pdbsum/5wpm PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5wpm 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=5wpm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5wpm OCA], [http://pdbe.org/5wpm PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5wpm RCSB], [http://www.ebi.ac.uk/pdbsum/5wpm PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5wpm ProSAT]</span></td></tr>
	</table>		</table>
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	</div>		</div>
	<div class="pdbe-citations 5wpm" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5wpm" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[GTPase KRas\|GTPase KRas]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Lee, S J]]		[[Category: Lee, S J]]
	[[Category: McGee, J H]]		[[Category: McGee, J H]]

OCA at 08:41, 10 January 2018

2018-01-10T08:41:12Z

←Older revision		Revision as of 08:41, 10 January 2018
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	== Function ==		== Function ==
	[[http://www.uniprot.org/uniprot/RASK_HUMAN RASK_HUMAN]] Ras proteins bind GDP/GTP and possess intrinsic GTPase activity.		[[http://www.uniprot.org/uniprot/RASK_HUMAN RASK_HUMAN]] Ras proteins bind GDP/GTP and possess intrinsic GTPase activity.
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The Ras proteins are aberrantly activated in a wide range of human cancers, often endowing tumors with aggressive properties and resistance to therapy. Decades of effort to develop direct Ras inhibitors for clinical use have thus far failed, largely because of a lack of adequate small-molecule binding pockets on the Ras surface. Here, we report the discovery of Ras-binding miniproteins from a naive library, and their evolution to afford versions with mid-picomolar affinity to Ras. A series of biochemical experiments indicated that these miniproteins bind to the Ras effector domain as dimers, and high-resolution crystal structures revealed that these miniprotein dimers bind Ras in an unprecedented mode, in which the Ras effector domain is remodeled to expose an extended pocket that connects two isolated pockets previously found to engage small-molecule ligands. We also report a Ras point mutant that stabilizes the protein in the open conformation trapped by these miniproteins. These findings provide new tools for studying Ras structure and function, and present opportunities for the development of both miniprotein and small-molecule inhibitors that directly target the Ras proteins.
		+
		+	Exceptionally high-affinity Ras binders that remodel its effector domain.,McGee JH, Shim SY, Lee SJ, Swanson PK, Jiang Y, Durney MA, Verdine GL J Biol Chem. 2017 Dec 27. pii: M117.816348. doi: 10.1074/jbc.M117.816348. PMID:29282294<ref>PMID:29282294</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 5wpm" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>

OCA at 05:49, 3 January 2018

2018-01-03T05:49:28Z

←Older revision		Revision as of 05:49, 3 January 2018
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-	'''Unreleased structure'''

-	~~The entry~~ 5wpm ~~is ON HOLD until Paper Publication~~	+	==KRas G12V, bound to GppNHp and miniprotein 225-11(A30R)==
-		+	<StructureSection load='5wpm' size='340' side='right' caption='[[5wpm]], [[Resolution\|resolution]] 1.72Å' scene=''>
-	~~Authors~~: ~~Lee, S~~.-J., ~~Shim~~, S.Y., ~~McGee~~, J.H., ~~Verdine~~, G.L.	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[5wpm]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5WPM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5WPM FirstGlance]. <br>
-	~~Description~~: ~~KRas G12V, bound~~ to ~~GppNHp~~ and ~~miniprotein 225~~-11(~~A30R~~)	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GNP:PHOSPHOAMINOPHOSPHONIC+ACID-GUANYLATE+ESTER'>GNP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
-	[[Category: ~~Unreleased Structures~~]]	+	<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=5wpm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5wpm OCA], [http://pdbe.org/5wpm PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5wpm RCSB], [http://www.ebi.ac.uk/pdbsum/5wpm PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5wpm ProSAT]</span></td></tr>
-	[[Category: ~~Mcgee~~, J.H]]	+	</table>
-	[[Category: ~~Lee~~, S~~.-J~~]]	+	== Disease ==
-	[[Category: Verdine, G.L]]	+	[[http://www.uniprot.org/uniprot/RASK_HUMAN RASK_HUMAN]] Defects in KRAS are a cause of acute myelogenous leukemia (AML) [MIM:[http://omim.org/entry/601626 601626]]. AML is a malignant disease in which hematopoietic precursors are arrested in an early stage of development.<ref>PMID:8955068</ref> Defects in KRAS are a cause of juvenile myelomonocytic leukemia (JMML) [MIM:[http://omim.org/entry/607785 607785]]. JMML is a pediatric myelodysplastic syndrome that constitutes approximately 30% of childhood cases of myelodysplastic syndrome (MDS) and 2% of leukemia. It is characterized by leukocytosis with tissue infiltration and in vitro hypersensitivity of myeloid progenitors to granulocyte-macrophage colony stimulating factor. Defects in KRAS are the cause of Noonan syndrome type 3 (NS3) [MIM:[http://omim.org/entry/609942 609942]]. Noonan syndrome (NS) [MIM:[http://omim.org/entry/163950 163950]] is a disorder characterized by dysmorphic facial features, short stature, hypertelorism, cardiac anomalies, deafness, motor delay, and a bleeding diathesis. It is a genetically heterogeneous and relatively common syndrome, with an estimated incidence of 1 in 1000-2500 live births. Rarely, NS is associated with juvenile myelomonocytic leukemia (JMML). NS3 inheritance is autosomal dominant.<ref>PMID:16773572</ref> <ref>PMID:16474405</ref> <ref>PMID:17468812</ref> <ref>PMID:17056636</ref> <ref>PMID:19396835</ref> <ref>PMID:20949621</ref> Defects in KRAS are a cause of gastric cancer (GASC) [MIM:[http://omim.org/entry/613659 613659]]; also called gastric cancer intestinal or stomach cancer. Gastric cancer is a malignant disease which starts in the stomach, can spread to the esophagus or the small intestine, and can extend through the stomach wall to nearby lymph nodes and organs. It also can metastasize to other parts of the body. The term gastric cancer or gastric carcinoma refers to adenocarcinoma of the stomach that accounts for most of all gastric malignant tumors. Two main histologic types are recognized, diffuse type and intestinal type carcinomas. Diffuse tumors are poorly differentiated infiltrating lesions, resulting in thickening of the stomach. In contrast, intestinal tumors are usually exophytic, often ulcerating, and associated with intestinal metaplasia of the stomach, most often observed in sporadic disease.<ref>PMID:3034404</ref> <ref>PMID:7773929</ref> <ref>PMID:14534542</ref> Note=Defects in KRAS are a cause of pylocytic astrocytoma (PA). Pylocytic astrocytomas are neoplasms of the brain and spinal cord derived from glial cells which vary from histologically benign forms to highly anaplastic and malignant tumors.<ref>PMID:8439212</ref> Defects in KRAS are a cause of cardiofaciocutaneous syndrome (CFC syndrome) [MIM:[http://omim.org/entry/115150 115150]]; also known as cardio-facio-cutaneous syndrome. CFC syndrome is characterized by a distinctive facial appearance, heart defects and mental retardation. Heart defects include pulmonic stenosis, atrial septal defects and hypertrophic cardiomyopathy. Some affected individuals present with ectodermal abnormalities such as sparse, friable hair, hyperkeratotic skin lesions and a generalized ichthyosis-like condition. Typical facial features are similar to Noonan syndrome. They include high forehead with bitemporal constriction, hypoplastic supraorbital ridges, downslanting palpebral fissures, a depressed nasal bridge, and posteriorly angulated ears with prominent helices. The inheritance of CFC syndrome is autosomal dominant. Note=KRAS mutations are involved in cancer development.
-	[[Category: ~~Shim, S.Y~~]]	+	== Function ==
		+	[[http://www.uniprot.org/uniprot/RASK_HUMAN RASK_HUMAN]] Ras proteins bind GDP/GTP and possess intrinsic GTPase activity.
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Lee, S J]]
		+	[[Category: McGee, J H]]
		+	[[Category: Shim, S Y]]
		+	[[Category: Verdine, G L]]
		+	[[Category: Complex]]
		+	[[Category: Inhibitor]]
		+	[[Category: Signaling protein]]

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

2017-09-27T15:03:53Z

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

←Older revision

Revision as of 15:03, 27 September 2017

OCA: New page: '''Unreleased structure''' The entry 5wpm is ON HOLD until Paper Publication Authors: Lee, S.-J., Shim, S.Y., McGee, J.H., Verdine, G.L. Description: KRas G12V, bound to GppNHp and min...

2017-09-27T15:03:52Z

New page: '''Unreleased structure''' The entry 5wpm is ON HOLD until Paper Publication Authors: Lee, S.-J., Shim, S.Y., McGee, J.H., Verdine, G.L. Description: KRas G12V, bound to GppNHp and min...

New page

'''Unreleased structure'''

The entry 5wpm is ON HOLD until Paper Publication

Authors: Lee, S.-J., Shim, S.Y., McGee, J.H., Verdine, G.L.

Description: KRas G12V, bound to GppNHp and miniprotein 225-11(A30R)
[[Category: Unreleased Structures]]
[[Category: Mcgee, J.H]]
[[Category: Lee, S.-J]]
[[Category: Verdine, G.L]]
[[Category: Shim, S.Y]]