OCA at 15:33, 28 August 2019

OCA — Wed, 28 Aug 2019 15:33:15 GMT

←Older revision		Revision as of 15:33, 28 August 2019
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-	'''Unreleased structure'''

-	~~The entry~~ 6p8x is ~~ON HOLD until Paper Publication~~	+	==Crystal structure of human KRAS G12C covalently bound to an acryloylazetidine acetamide inhibitor.==
-		+	<StructureSection load='6p8x' size='340' side='right'caption='[[6p8x]], [[Resolution\|resolution]] 2.11Å' scene=''>
-	~~Authors~~: ~~Mohr~~, C.	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[6p8x]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6P8X OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6P8X FirstGlance]. <br>
-	~~Description~~: ~~Crystal structure~~ of ~~human~~ KRAS ~~G12C covalently bound~~ to an ~~acryloylazetidine acetamide inhibitor~~.	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene>, <scene name='pdbligand=O5V:2-[4-bromo-2-(3-phenyl-2,5-dihydro-1H-pyrrole-1-carbonyl)phenoxy]-N-(1-propanoylazetidin-3-yl)acetamide'>O5V</scene></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[6p8w\|6p8w]]</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=6p8x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6p8x OCA], [http://pdbe.org/6p8x PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6p8x RCSB], [http://www.ebi.ac.uk/pdbsum/6p8x PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6p8x ProSAT]</span></td></tr>
		+	</table>
		+	== Disease ==
		+	[[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.
		+	== 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: Large Structures]]
	[[Category: Mohr, C]]		[[Category: Mohr, C]]
		+	[[Category: Gtpase]]
		+	[[Category: Inhibitor]]
		+	[[Category: Signaling protein]]
		+	[[Category: Signaling protein-inhibitor complex]]

OCA: Protected "6p8x" [edit=sysop:move=sysop]

OCA — Wed, 19 Jun 2019 04:17:30 GMT

Protected "6p8x" [edit=sysop:move=sysop]

←Older revision

Revision as of 04:17, 19 June 2019

OCA: New page: '''Unreleased structure''' The entry 6p8x is ON HOLD until Paper Publication Authors: Mohr, C. Description: Crystal structure of human KRAS G12C covalently bound to an acryloylazetidin...

OCA — Wed, 19 Jun 2019 04:17:28 GMT

New page: '''Unreleased structure''' The entry 6p8x is ON HOLD until Paper Publication Authors: Mohr, C. Description: Crystal structure of human KRAS G12C covalently bound to an acryloylazetidin...

New page

'''Unreleased structure'''

The entry 6p8x is ON HOLD until Paper Publication

Authors: Mohr, C.

Description: Crystal structure of human KRAS G12C covalently bound to an acryloylazetidine acetamide inhibitor.
[[Category: Unreleased Structures]]
[[Category: Mohr, C]]

6p8x - Revision history

OCA at 15:33, 28 August 2019

OCA: Protected "6p8x" [edit=sysop:move=sysop]

OCA: New page: '''Unreleased structure''' The entry 6p8x is ON HOLD until Paper Publication Authors: Mohr, C. Description: Crystal structure of human KRAS G12C covalently bound to an acryloylazetidin...