View source for 5hhi


==Structure of human DNA polymerase beta Host-Guest complexed with CBZ-platinated N7-G==
<StructureSection load='5hhi' size='340' side='right'caption='[[5hhi]], [[Resolution|resolution]] 2.52&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5hhi]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5HHI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5HHI 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]] 2.517&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=61C:PLATINUM(4+)+CHLORIDE+AZANIDE+[2-(9H-CARBAZOL-9-YL)ETHYL]AZANIDE+(1 1 2 1)'>61C</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</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=5hhi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5hhi OCA], [https://pdbe.org/5hhi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5hhi RCSB], [https://www.ebi.ac.uk/pdbsum/5hhi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5hhi ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/DPOLB_HUMAN DPOLB_HUMAN] Repair polymerase that plays a key role in base-excision repair. Has 5'-deoxyribose-5-phosphate lyase (dRP lyase) activity that removes the 5' sugar phosphate and also acts as a DNA polymerase that adds one nucleotide to the 3' end of the arising single-nucleotide gap. Conducts 'gap-filling' DNA synthesis in a stepwise distributive fashion rather than in a processive fashion as for other DNA polymerases.<ref>PMID:9207062</ref> <ref>PMID:9572863</ref> <ref>PMID:11805079</ref> <ref>PMID:21362556</ref> 
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== Publication Abstract from PubMed ==
Cisplatin resistance is caused, in part, by the efficient removal of the helix-distorting cisplatin 1,2-intrastrand cross-links by nucleotide excision repair (NER) machinery. To make a platinum-DNA adduct that causes less helical distortion than the cisplatin 1,2-intrastrand adduct, we designed and synthesized a monofunctional platinum-carbazole conjugate (carbazoplatin). The 2.5 A crystal structure of carbazoplatin-DNA adduct revealed both the monoplatination of the N7 of a guanine (G) base and the intercalation into two G:C base pairs, while causing a minor distortion of the DNA helix. A 50-mer dsDNA containing a single carbazoplatin lesion was poorly processed by UvrABC endonuclease, the prokaryotic NER machinery that detects helical distortion and performs dual incision around the lesion. Our cell viability assay indicated that the cytotoxic pathways of carbazoplatin might be different from those of cisplatin; carbazoplatin was 5-8 times more cytotoxic than cisplatin against PANC-1 and MDA-MB-231 cancer cell lines.

Synthesis, structure, and biological evaluation of a platinum-carbazole conjugate.,Cheun Y, Koag MC, Naguib YW, Ouzon-Shubeita H, Cui Z, Pakotiprapha D, Lee S Chem Biol Drug Des. 2018 Jan;91(1):116-125. doi: 10.1111/cbdd.13062. Epub 2017, Jul 29. PMID:28649747<ref>PMID:28649747</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 5hhi" style="background-color:#fffaf0;"></div>

==See Also==
*[[DNA polymerase 3D structures|DNA polymerase 3D structures]]
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Synthetic construct]]
[[Category: Koag M-C]]
[[Category: Lee S]]