7p8p
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal structure of Fhit covalently bound to a nucleotide== | |
| + | <StructureSection load='7p8p' size='340' side='right'caption='[[7p8p]], [[Resolution|resolution]] 2.34Å' 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]] 2.34Å</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-[6-(2-chloranylethanoylamino)hexylamino]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. | ||
| - | + | 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> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </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]] | ||
Current revision
Crystal structure of Fhit covalently bound to a nucleotide
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