7p8p: Difference between revisions

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~~'''Unreleased structure'''~~

~~The entry~~ 7p8p is ~~ON HOLD until Paper~~ Publication

==Crystal structure of Fhit covalently bound to a nucleotide==

== Structural highlights ==

<table><tr><td colspan='2'>[[7p8p]] is a 4 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=7P8P OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7P8P 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]] 2.34Å</td></tr>

<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=6BI:[(2~{R},3~{S},4~{R},5~{R})-5-[6-(ethylamino)purin-9-yl]-3,4-bis(oxidanyl)oxolan-2-yl]methyl+dihydrogen+phosphate'>6BI</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=TRS:2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>TRS</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=7p8p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7p8p OCA], [https://pdbe.org/7p8p PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7p8p RCSB], [https://www.ebi.ac.uk/pdbsum/7p8p PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7p8p ProSAT]</span></td></tr>

</table>

== Disease ==

[https://www.uniprot.org/uniprot/FHIT_HUMAN FHIT_HUMAN] Note=A chromosomal aberration involving FHIT has been found in a lymphoblastoid cell line established from a family with renal cell carcinoma and thyroid carcinoma. Translocation t(3;8)(p14.2;q24.1) with RNF139. Although the 3p14.2 breakpoint has been shown to interrupt FHIT in its 5-prime non-coding region, it is unlikely that FHIT is causally related to renal or other malignancies.<ref>PMID:15007172</ref> Note=Associated with digestive tract cancers. Numerous tumor types are found to have aberrant forms of FHIT protein due to deletions in a coding region of chromosome 3p14.2 including the fragile site locus FRA3B.<ref>PMID:15007172</ref>

== Function ==

[https://www.uniprot.org/uniprot/FHIT_HUMAN FHIT_HUMAN] Cleaves A-5'-PPP-5'A to yield AMP and ADP. Possible tumor suppressor for specific tissues.<ref>PMID:8794732</ref>

== Publication Abstract from PubMed ==

The tumor suppressor protein fragile histidine triad (Fhit) is known to be associated with genomic instability and apoptosis. The tumor-suppressive function of Fhit depends on the interaction with the alarmone diadenosine triphosphate (Ap(3)A), a noncanonical nucleotide whose concentration increases upon cellular stress. How the Fhit-Ap(3)A complex exerts its signaling function is unknown. Here, guided by a chemical proteomics approach employing a synthetic stable Fhit-Ap(3)A complex, we found that the Fhit-Ap(3)A complex, but not Fhit or Ap(3)A alone, impedes translation. Our findings provide a mechanistic model in which Fhit translocates from the nucleolus into the cytosol upon stress to form an Fhit-Ap(3)A complex. The Fhit-Ap(3)A complex impedes translation both in vitro and in vivo, resulting in reduced cell viability. Overall, our findings provide a mechanistic model by which the tumor suppressor Fhit collaborates with the alarmone Ap(3)A to regulate cellular proliferation.

~~Authors~~:

Chemical Proteomics of the Tumor Suppressor Fhit Covalently Bound to the Cofactor Ap(3)A Elucidates Its Inhibitory Action on Translation.,Herzog D, Jansen J, Missun M, Diederichs K, Stengel F, Marx A J Am Chem Soc. 2022 May 18;144(19):8613-8623. doi: 10.1021/jacs.2c00815. Epub , 2022 May 6. PMID:35522782<ref>PMID:35522782</ref>

~~Description~~:

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

[[Category: ~~Unreleased~~ Structures]]

</div>

== References ==

__TOC__

</StructureSection>

[[Category: Homo sapiens]]

[[Category: Large Structures]]

[[Category: Diederichs K]]

[[Category: Herzog D]]

[[Category: Marx A]]

[[Category: Missun M]]

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@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 7p8p is ON HOLD  until Paper Publication
+==Crystal structure of Fhit covalently bound to a nucleotide==
+<StructureSection load='7p8p' size='340' side='right'caption='[[7p8p]], [[Resolution|resolution]] 2.34&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[7p8p]] is a 4 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=7P8P OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7P8P 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]] 2.34&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=6BI:[(2~{R},3~{S},4~{R},5~{R})-5-[6-(ethylamino)purin-9-yl]-3,4-bis(oxidanyl)oxolan-2-yl]methyl+dihydrogen+phosphate'>6BI</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=TRS:2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>TRS</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=7p8p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7p8p OCA], [https://pdbe.org/7p8p PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7p8p RCSB], [https://www.ebi.ac.uk/pdbsum/7p8p PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7p8p ProSAT]</span></td></tr>
+</table>
+== Disease ==
+[https://www.uniprot.org/uniprot/FHIT_HUMAN FHIT_HUMAN] Note=A chromosomal aberration involving FHIT has been found in a lymphoblastoid cell line established from a family with renal cell carcinoma and thyroid carcinoma. Translocation t(3;8)(p14.2;q24.1) with RNF139. Although the 3p14.2 breakpoint has been shown to interrupt FHIT in its 5-prime non-coding region, it is unlikely that FHIT is causally related to renal or other malignancies.<ref>PMID:15007172</ref>   Note=Associated with digestive tract cancers. Numerous tumor types are found to have aberrant forms of FHIT protein due to deletions in a coding region of chromosome 3p14.2 including the fragile site locus FRA3B.<ref>PMID:15007172</ref>
+== Function ==
+[https://www.uniprot.org/uniprot/FHIT_HUMAN FHIT_HUMAN] Cleaves A-5'-PPP-5'A to yield AMP and ADP. Possible tumor suppressor for specific tissues.<ref>PMID:8794732</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+The tumor suppressor protein fragile histidine triad (Fhit) is known to be associated with genomic instability and apoptosis. The tumor-suppressive function of Fhit depends on the interaction with the alarmone diadenosine triphosphate (Ap(3)A), a noncanonical nucleotide whose concentration increases upon cellular stress. How the Fhit-Ap(3)A complex exerts its signaling function is unknown. Here, guided by a chemical proteomics approach employing a synthetic stable Fhit-Ap(3)A complex, we found that the Fhit-Ap(3)A complex, but not Fhit or Ap(3)A alone, impedes translation. Our findings provide a mechanistic model in which Fhit translocates from the nucleolus into the cytosol upon stress to form an Fhit-Ap(3)A complex. The Fhit-Ap(3)A complex impedes translation both in vitro and in vivo, resulting in reduced cell viability. Overall, our findings provide a mechanistic model by which the tumor suppressor Fhit collaborates with the alarmone Ap(3)A to regulate cellular proliferation.
-Authors:
+Chemical Proteomics of the Tumor Suppressor Fhit Covalently Bound to the Cofactor Ap(3)A Elucidates Its Inhibitory Action on Translation.,Herzog D, Jansen J, Missun M, Diederichs K, Stengel F, Marx A J Am Chem Soc. 2022 May 18;144(19):8613-8623. doi: 10.1021/jacs.2c00815. Epub , 2022 May 6. PMID:35522782<ref>PMID:35522782</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 7p8p" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Diederichs K]]
+[[Category: Herzog D]]
+[[Category: Marx A]]
+[[Category: Missun M]]