3co3

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<StructureSection load='3co3' size='340' side='right'caption='[[3co3]], [[Resolution|resolution]] 2.16&Aring;' scene=''>
<StructureSection load='3co3' size='340' side='right'caption='[[3co3]], [[Resolution|resolution]] 2.16&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[3co3]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3CO3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3CO3 FirstGlance]. <br>
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<table><tr><td colspan='2'>[[3co3]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3CO3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3CO3 FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=C7P:CIS-DIAMMINE(PYRIDINE)CHLOROPLATINUM(II)'>C7P</scene></td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.16&#8491;</td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3co3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3co3 OCA], [http://pdbe.org/3co3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3co3 RCSB], [http://www.ebi.ac.uk/pdbsum/3co3 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3co3 ProSAT]</span></td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=C7P:CIS-DIAMMINE(PYRIDINE)CHLOROPLATINUM(II)'>C7P</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3co3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3co3 OCA], [https://pdbe.org/3co3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3co3 RCSB], [https://www.ebi.ac.uk/pdbsum/3co3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3co3 ProSAT]</span></td></tr>
</table>
</table>
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<div style="background-color:#fffaf0;">
 
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== Publication Abstract from PubMed ==
 
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We have identified unique chemical and biological properties of a cationic monofunctional platinum(II) complex, cis-diammine(pyridine)chloroplatinum(II), cis-[Pt(NH(3))(2)(py)Cl](+) or cDPCP, a coordination compound previously identified to have significant anticancer activity in a mouse tumor model. This compound is an excellent substrate for organic cation transporters 1 and 2, also designated SLC22A1 and SLC22A2, respectively. These transporters are abundantly expressed in human colorectal cancers, where they mediate uptake of oxaliplatin, cis-[Pt(DACH)(oxalate)] (DACH = trans-R,R-1,2-diaminocyclohexane), an FDA-approved first-line therapy for colorectal cancer. Unlike oxaliplatin, however, cDPCP binds DNA monofunctionally, as revealed by an x-ray crystal structure of cis-{Pt(NH(3))(2)(py)}(2+) bound to the N7 atom of a single guanosine residue in a DNA dodecamer duplex. Although the quaternary structure resembles that of B-form DNA, there is a base-pair step to the 5' side of the Pt adduct with abnormally large shift and slide values, features characteristic of cisplatin intrastrand cross-links. cDPCP effectively blocks transcription from DNA templates carrying adducts of the complex, unlike DNA lesions of other monofunctional platinum(II) compounds like {Pt(dien)}(2+). cDPCP-DNA adducts are removed by the nucleotide excision repair apparatus, albeit much less efficiently than bifunctional platinum-DNA intrastrand cross-links. These exceptional characteristics indicate that cDPCP and related complexes merit consideration as therapeutic options for treating colorectal and other cancers bearing appropriate cation transporters.
 
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cis-Diammine(pyridine)chloroplatinum(II), a monofunctional platinum(II) antitumor agent: Uptake, structure, function, and prospects.,Lovejoy KS, Todd RC, Zhang S, McCormick MS, D'Aquino JA, Reardon JT, Sancar A, Giacomini KM, Lippard SJ Proc Natl Acad Sci U S A. 2008 Jul 1;105(26):8902-7. Epub 2008 Jun 25. PMID:18579768<ref>PMID:18579768</ref>
 
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 
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</div>
 
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<div class="pdbe-citations 3co3" style="background-color:#fffaf0;"></div>
 
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== References ==
 
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<references/>
 
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Large Structures]]
[[Category: Large Structures]]
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[[Category: Aquino, J A.D]]
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[[Category: D'Aquino JA]]
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[[Category: Giacomini, K M]]
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[[Category: Giacomini KM]]
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[[Category: Lippard, S J]]
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[[Category: Lippard SJ]]
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[[Category: Lovejoy, K S]]
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[[Category: Lovejoy KS]]
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[[Category: McCormick, M S]]
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[[Category: McCormick MS]]
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[[Category: Reardon, J T]]
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[[Category: Reardon JT]]
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[[Category: Sancar, A]]
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[[Category: Sancar A]]
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[[Category: Todd, R C]]
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[[Category: Todd RC]]
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[[Category: Zhang, S]]
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[[Category: Zhang S]]
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[[Category: Cisplatin]]
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[[Category: Dna]]
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[[Category: Monofunctional pt compound]]
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[[Category: Platinum-dna duplex]]
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Current revision

X-Ray Crystal Structure of a Monofunctional Platinum-DNA Adduct, cis-{Pt(NH3)2(pyridine)}2+ Bound to Deoxyguanosine in a Dodecamer Duplex

PDB ID 3co3

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