View source for 8oo4


==X-ray structure of the adduct formed upon reaction of cisplatin with human angiogenin after 1 month soaking==
<StructureSection load='8oo4' size='340' side='right'caption='[[8oo4]], [[Resolution|resolution]] 1.99&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8oo4]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8OO4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8OO4 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]] 1.99&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NH3:AMMONIA'>NH3</scene>, <scene name='pdbligand=PT:PLATINUM+(II)+ION'>PT</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=8oo4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8oo4 OCA], [https://pdbe.org/8oo4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8oo4 RCSB], [https://www.ebi.ac.uk/pdbsum/8oo4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8oo4 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/ANGI_GORGO ANGI_GORGO] Ribonuclease that cleaves tRNA within anticodon loops to produce tRNA-derived stress-induced fragments (tiRNAs) which inhibit protein synthesis and triggers the assembly of stress granules (SGs). Binds to actin on the surface of endothelial cells; once bound, angiogenin is endocytosed and translocated to the nucleus. Stimulates ribosomal RNA synthesis including that containing the initiation site sequences of 45S rRNA. Angiogenin induces vascularization of normal and malignant tissues. Angiogenic activity is regulated by interaction with RNH1 in vivo.[UniProtKB:P03950]
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== Publication Abstract from PubMed ==
Cisplatin (CisPt), a platinum-based chemotherapeutic widely used in the treatment of various cancers, has multiple mechanisms of action, including nuclear DNA (nDNA) and mitochondrial DNA (mDNA) damage and cytoskeletal perturbations affecting, in turn, the membrane transporter activity. CisPt binding to proteins and enzymes may modulate its biochemical mechanism of action and is associated with cancer cell resistance to the drug. In this work, we investigate the interaction between cisplatin and angiogenin (Ang), a protein strongly expressed in many types of cancer and a potent angiogenic factor. The adduct formed upon reaction of CisPt with Ang (Ang@CisPt) was characterized by X-ray crystallography to evidence the exact platination site and by UV-visible (UV-vis) absorption and circular dichroism (CD) spectroscopies to shed light on any possible change in the protein conformation. Furthermore, high-resolution electrospray ionization (ESI) mass spectrometry was utilized to evaluate the Ang : CisPt stoichiometry of the Ang@CisPt adduct. The effect of the Ang@CisPt adduct on a prostate cancer cell line (PC-3) was tested by colorimetric assays in terms of cell viability, at both levels of nuclear and mitochondrial damage, and reactive oxygen species (ROS) production. Cellular imaging by laser scanning confocal microscopy (LSM) was utilized to scrutinize the cytoskeleton actin reorganization and the lysosome and mitochondria organelle perturbation. These studies highlight the possibility of new molecular pathways and targets for CisPt activity.

Cisplatin binding to angiogenin protein: new molecular pathways and targets for the drug's anticancer activity.,Ferraro G, Sanfilippo V, Chiaverini L, Satriano C, Marzo T, Merlino A, La Mendola D Dalton Trans. 2023 Jul 4;52(26):9058-9067. doi: 10.1039/d3dt01517c. PMID:37337706<ref>PMID:37337706</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8oo4" style="background-color:#fffaf0;"></div>

==See Also==
*[[Ribonuclease 3D structures|Ribonuclease 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Escherichia coli]]
[[Category: Large Structures]]
[[Category: Ferraro G]]
[[Category: Merlino A]]