7ztl: Difference between revisions

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'''Unreleased structure'''


The entry 7ztl is ON HOLD
==Crystal structure of a covalently linked Aurora-A N-Myc complex==
<StructureSection load='7ztl' size='340' side='right'caption='[[7ztl]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7ztl]] 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=7ZTL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7ZTL FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.9&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=BCN:BICINE'>BCN</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=JWG:4-(3-hydroxy-3-oxopropylamino)-4-oxidanylidene-butanoic+acid'>JWG</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</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=7ztl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ztl OCA], [https://pdbe.org/7ztl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ztl RCSB], [https://www.ebi.ac.uk/pdbsum/7ztl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ztl ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/MYCN_HUMAN MYCN_HUMAN] Unilateral retinoblastoma;Neuroblastoma;Feingold syndrome type 1. Amplification of the N-MYC gene is associated with a variety of human tumors, most frequently neuroblastoma, where the level of amplification appears to increase as the tumor progresses.<ref>PMID:2834684</ref>  The disease is caused by mutations affecting the gene represented in this entry.
== Function ==
[https://www.uniprot.org/uniprot/MYCN_HUMAN MYCN_HUMAN] Positively regulates the transcription of NCYM in neuroblastoma cells (PubMed:24391509).<ref>PMID:24391509</ref>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Formation of the Aurora-A-MYCN complex increases levels of the oncogenic transcription factor MYCN in neuroblastoma cells by abrogating its degradation through the ubiquitin proteasome system. While some small-molecule inhibitors of Aurora-A were shown to destabilize MYCN, clinical trials have not been satisfactory to date. MYCN itself is considered to be ;undruggable' due to its large intrinsically disordered regions. Targeting the Aurora-A-MYCN complex rather than Aurora-A or MYCN alone will open new possibilities for drug development and screening campaigns. To overcome the challenges that a ternary system composed of Aurora-A, MYCN and a small molecule entails, a covalently cross-linked construct of the Aurora-A-MYCN complex was designed, expressed and characterized, thus enabling screening and design campaigns to identify selective binders.


Authors:  
Crystal structure of a covalently linked Aurora-A-MYCN complex.,Diebold M, Schonemann L, Eilers M, Sotriffer C, Schindelin H Acta Crystallogr D Struct Biol. 2023 Jan 1;79(Pt 1):1-9. doi: , 10.1107/S2059798322011433. Epub 2023 Jan 1. PMID:36601802<ref>PMID:36601802</ref>


Description:  
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
[[Category: Unreleased Structures]]
</div>
<div class="pdbe-citations 7ztl" style="background-color:#fffaf0;"></div>
 
==See Also==
*[[Serine/threonine protein kinase 3D structures|Serine/threonine protein kinase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Diebold M]]
[[Category: Schindelin H]]

Latest revision as of 17:18, 6 November 2024

Crystal structure of a covalently linked Aurora-A N-Myc complexCrystal structure of a covalently linked Aurora-A N-Myc complex

Structural highlights

7ztl is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 1.9Å
Ligands:, , , , , ,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

MYCN_HUMAN Unilateral retinoblastoma;Neuroblastoma;Feingold syndrome type 1. Amplification of the N-MYC gene is associated with a variety of human tumors, most frequently neuroblastoma, where the level of amplification appears to increase as the tumor progresses.[1] The disease is caused by mutations affecting the gene represented in this entry.

Function

MYCN_HUMAN Positively regulates the transcription of NCYM in neuroblastoma cells (PubMed:24391509).[2]

Publication Abstract from PubMed

Formation of the Aurora-A-MYCN complex increases levels of the oncogenic transcription factor MYCN in neuroblastoma cells by abrogating its degradation through the ubiquitin proteasome system. While some small-molecule inhibitors of Aurora-A were shown to destabilize MYCN, clinical trials have not been satisfactory to date. MYCN itself is considered to be ;undruggable' due to its large intrinsically disordered regions. Targeting the Aurora-A-MYCN complex rather than Aurora-A or MYCN alone will open new possibilities for drug development and screening campaigns. To overcome the challenges that a ternary system composed of Aurora-A, MYCN and a small molecule entails, a covalently cross-linked construct of the Aurora-A-MYCN complex was designed, expressed and characterized, thus enabling screening and design campaigns to identify selective binders.

Crystal structure of a covalently linked Aurora-A-MYCN complex.,Diebold M, Schonemann L, Eilers M, Sotriffer C, Schindelin H Acta Crystallogr D Struct Biol. 2023 Jan 1;79(Pt 1):1-9. doi: , 10.1107/S2059798322011433. Epub 2023 Jan 1. PMID:36601802[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

See Also

References

  1. ↑ Ibson JM, Rabbitts PH. Sequence of a germ-line N-myc gene and amplification as a mechanism of activation. Oncogene. 1988 Apr;2(4):399-402. PMID:2834684
  2. ↑ Suenaga Y, Islam SM, Alagu J, Kaneko Y, Kato M, Tanaka Y, Kawana H, Hossain S, Matsumoto D, Yamamoto M, Shoji W, Itami M, Shibata T, Nakamura Y, Ohira M, Haraguchi S, Takatori A, Nakagawara A. NCYM, a Cis-antisense gene of MYCN, encodes a de novo evolved protein that inhibits GSK3beta resulting in the stabilization of MYCN in human neuroblastomas. PLoS Genet. 2014 Jan;10(1):e1003996. doi: 10.1371/journal.pgen.1003996. Epub 2014, Jan 2. PMID:24391509 doi:http://dx.doi.org/10.1371/journal.pgen.1003996
  3. ↑ Diebold M, Schönemann L, Eilers M, Sotriffer C, Schindelin H. Crystal structure of a covalently linked Aurora-A-MYCN complex. Acta Crystallogr D Struct Biol. 2023 Jan 1;79(Pt 1):1-9. PMID:36601802 doi:10.1107/S2059798322011433

7ztl, resolution 1.90Å

Drag the structure with the mouse to rotate

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