OCA at 06:44, 8 February 2023

OCA — Wed, 08 Feb 2023 06:44:04 GMT

←Older revision		Revision as of 06:44, 8 February 2023
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-	'''Unreleased structure'''

-	The entry ~~7ygi~~ is ~~ON HOLD~~ ~~until Paper~~ Publication	+	==Crystal structure of p53 DBD domain in complex with azurin==
		+	<StructureSection load='7ygi' size='340' side='right'caption='[[7ygi]], [[Resolution\|resolution]] 2.10Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[7ygi]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Pseudomonas_aeruginosa_PAO1 Pseudomonas aeruginosa PAO1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7YGI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7YGI FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=7ygi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ygi OCA], [https://pdbe.org/7ygi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ygi RCSB], [https://www.ebi.ac.uk/pdbsum/7ygi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ygi ProSAT]</span></td></tr>
		+	</table>
		+	== Disease ==
		+	[https://www.uniprot.org/uniprot/P53_HUMAN P53_HUMAN] Note=TP53 is found in increased amounts in a wide variety of transformed cells. TP53 is frequently mutated or inactivated in about 60% of cancers. TP53 defects are found in Barrett metaplasia a condition in which the normally stratified squamous epithelium of the lower esophagus is replaced by a metaplastic columnar epithelium. The condition develops as a complication in approximately 10% of patients with chronic gastroesophageal reflux disease and predisposes to the development of esophageal adenocarcinoma. Defects in TP53 are a cause of esophageal cancer (ESCR) [MIM:[https://omim.org/entry/133239 133239]. Defects in TP53 are a cause of Li-Fraumeni syndrome (LFS) [MIM:[https://omim.org/entry/151623 151623]. LFS is an autosomal dominant familial cancer syndrome that in its classic form is defined by the existence of a proband affected by a sarcoma before 45 years with a first degree relative affected by any tumor before 45 years and another first degree relative with any tumor before 45 years or a sarcoma at any age. Other clinical definitions for LFS have been proposed (PubMed:8118819 and PubMed:8718514) and called Li-Fraumeni like syndrome (LFL). In these families affected relatives develop a diverse set of malignancies at unusually early ages. Four types of cancers account for 80% of tumors occurring in TP53 germline mutation carriers: breast cancers, soft tissue and bone sarcomas, brain tumors (astrocytomas) and adrenocortical carcinomas. Less frequent tumors include choroid plexus carcinoma or papilloma before the age of 15, rhabdomyosarcoma before the age of 5, leukemia, Wilms tumor, malignant phyllodes tumor, colorectal and gastric cancers.<ref>PMID:10570149</ref> <ref>PMID:1933902</ref> <ref>PMID:1978757</ref> <ref>PMID:2259385</ref> <ref>PMID:1737852</ref> <ref>PMID:1565144</ref> <ref>PMID:7887414</ref> <ref>PMID:8825920</ref> <ref>PMID:9452042</ref> <ref>PMID:10484981</ref> Defects in TP53 are involved in head and neck squamous cell carcinomas (HNSCC) [MIM:[https://omim.org/entry/275355 275355]; also known as squamous cell carcinoma of the head and neck. Defects in TP53 are a cause of lung cancer (LNCR) [MIM:[https://omim.org/entry/211980 211980]. LNCR is a common malignancy affecting tissues of the lung. The most common form of lung cancer is non-small cell lung cancer (NSCLC) that can be divided into 3 major histologic subtypes: squamous cell carcinoma, adenocarcinoma, and large cell lung cancer. NSCLC is often diagnosed at an advanced stage and has a poor prognosis. Defects in TP53 are a cause of choroid plexus papilloma (CPLPA) [MIM:[https://omim.org/entry/260500 260500]. Choroid plexus papilloma is a slow-growing benign tumor of the choroid plexus that often invades the leptomeninges. In children it is usually in a lateral ventricle but in adults it is more often in the fourth ventricle. Hydrocephalus is common, either from obstruction or from tumor secretion of cerebrospinal fluid. If it undergoes malignant transformation it is called a choroid plexus carcinoma. Primary choroid plexus tumors are rare and usually occur in early childhood.<ref>PMID:12085209</ref> Defects in TP53 are a cause of adrenocortical carcinoma (ADCC) [MIM:[https://omim.org/entry/202300 202300]. ADCC is a rare childhood tumor of the adrenal cortex. It occurs with increased frequency in patients with the Beckwith-Wiedemann syndrome and is a component tumor in Li-Fraumeni syndrome.<ref>PMID:11481490</ref> Defects in TP53 are the cause of susceptibility to basal cell carcinoma 7 (BCC7) [MIM:[https://omim.org/entry/614740 614740]. A common malignant skin neoplasm that typically appears on hair-bearing skin, most commonly on sun-exposed areas. It is slow growing and rarely metastasizes, but has potentialities for local invasion and destruction. It usually develops as a flat, firm, pale area that is small, raised, pink or red, translucent, shiny, and waxy, and the area may bleed following minor injury. Tumor size can vary from a few millimeters to several centimeters in diameter.<ref>PMID:21946351</ref>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/P53_HUMAN P53_HUMAN] Acts as a tumor suppressor in many tumor types; induces growth arrest or apoptosis depending on the physiological circumstances and cell type. Involved in cell cycle regulation as a trans-activator that acts to negatively regulate cell division by controlling a set of genes required for this process. One of the activated genes is an inhibitor of cyclin-dependent kinases. Apoptosis induction seems to be mediated either by stimulation of BAX and FAS antigen expression, or by repression of Bcl-2 expression. In cooperation with mitochondrial PPIF is involved in activating oxidative stress-induced necrosis; te function is largely independent of transcription. Induces the transcription of long intergenic non-coding RNA p21 (lincRNA-p21) and lincRNA-Mkln1. LincRNA-p21 participates in TP53-dependent transcriptional repression leading to apoptosis and seem to have to effect on cell-cycle regulation. Implicated in Notch signaling cross-over. Prevents CDK7 kinase activity when associated to CAK complex in response to DNA damage, thus stopping cell cycle progression. Isoform 2 enhances the transactivation activity of isoform 1 from some but not all TP53-inducible promoters. Isoform 4 suppresses transactivation activity and impairs growth suppression mediated by isoform 1. Isoform 7 inhibits isoform 1-mediated apoptosis.<ref>PMID:9840937</ref> <ref>PMID:11025664</ref> <ref>PMID:12810724</ref> <ref>PMID:15186775</ref> <ref>PMID:15340061</ref> <ref>PMID:17317671</ref> <ref>PMID:17349958</ref> <ref>PMID:19556538</ref> <ref>PMID:20673990</ref> <ref>PMID:20959462</ref> <ref>PMID:22726440</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Tumor suppressor p53 prevents tumorigenesis by promoting cell cycle arrest and apoptosis through transcriptional regulation. Dysfunction of p53 occurs frequently in human cancers. Thus, p53 becomes one of the most promising targets for anticancer treatment. A bacterial effector protein azurin triggers tumor suppression by stabilizing p53 and elevating its basal level. However, the structural and mechanistic basis of azurin-mediated tumor suppression remains elusive. Here we report the atomic details of azurin-mediated p53 stabilization by combining X-ray crystallography with nuclear magnetic resonance. Structural and mutagenic analysis reveals that the p28 region of azurin, which corresponds to a therapeutic peptide, significantly contributes to p53 binding. This binding stabilizes p53 by disrupting COP1-mediated p53 ubiquitination and degradation. Using the structure-based design, we obtain several affinity-enhancing mutants that enable amplifying the effect of azurin-induced apoptosis. Our findings highlight how the structure of the azurin-p53 complex can be leveraged to design azurin derivatives for cancer therapy.

-	~~Authors~~:	+	Structural basis of bacterial effector protein azurin targeting tumor suppressor p53 and inhibiting its ubiquitination.,Hu J, Jiang W, Zuo J, Shi D, Chen X, Yang X, Zhang W, Ma L, Liu Z, Xing Q Commun Biol. 2023 Jan 17;6(1):59. doi: 10.1038/s42003-023-04458-1. PMID:36650277<ref>PMID:36650277</ref>

-	~~Description~~:	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased~~ Structures]]	+	</div>
		+	<div class="pdbe-citations 7ygi" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Homo sapiens]]
		+	[[Category: Large Structures]]
		+	[[Category: Pseudomonas aeruginosa PAO1]]
		+	[[Category: Chen XQ]]
		+	[[Category: Hu JJ]]
		+	[[Category: Jiang WX]]
		+	[[Category: Liu Z]]
		+	[[Category: Ma LX]]
		+	[[Category: Xing Q]]
		+	[[Category: Zuo JQ]]

OCA at 04:59, 7 December 2022

OCA — Wed, 07 Dec 2022 04:59:45 GMT

←Older revision		Revision as of 04:59, 7 December 2022
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	'''Unreleased structure'''		'''Unreleased structure'''

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

	Authors:		Authors:

OCA at 08:16, 30 November 2022

OCA — Wed, 30 Nov 2022 08:16:56 GMT

←Older revision		Revision as of 08:16, 30 November 2022
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 7ygi is ON HOLD ~~until Paper Publication~~	+	The entry 7ygi is ON HOLD

	Authors:		Authors:

OCA at 05:17, 31 August 2022

OCA — Wed, 31 Aug 2022 05:17:43 GMT

←Older revision		Revision as of 05:17, 31 August 2022
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	'''Unreleased structure'''		'''Unreleased structure'''

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

	Authors:		Authors:

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

OCA — Wed, 20 Jul 2022 03:59:55 GMT

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

←Older revision

Revision as of 03:59, 20 July 2022

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

OCA — Wed, 20 Jul 2022 03:59:53 GMT

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

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