6d0m
From Proteopedia
(Difference between revisions)
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| - | '''Unreleased structure''' | ||
| - | + | ==Polymerase Eta post-insertion binary complex with cytarabine (AraC)== | |
| + | <StructureSection load='6d0m' size='340' side='right' caption='[[6d0m]], [[Resolution|resolution]] 1.83Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[6d0m]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6D0M OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6D0M FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr> | ||
| + | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CAR:CYTOSINE+ARABINOSE-5-PHOSPHATE'>CAR</scene></td></tr> | ||
| + | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/DNA-directed_DNA_polymerase DNA-directed DNA polymerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.7 2.7.7.7] </span></td></tr> | ||
| + | <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=6d0m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6d0m OCA], [http://pdbe.org/6d0m PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6d0m RCSB], [http://www.ebi.ac.uk/pdbsum/6d0m PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6d0m ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Disease == | ||
| + | [[http://www.uniprot.org/uniprot/POLH_HUMAN POLH_HUMAN]] Defects in POLH are the cause of xeroderma pigmentosum variant type (XPV) [MIM:[http://omim.org/entry/278750 278750]]; also designated as XP-V. Xeroderma pigmentosum (XP) is an autosomal recessive disease due to deficient nucleotide excision repair. It is characterized by hypersensitivity of the skin to sunlight, followed by high incidence of skin cancer and frequent neurologic abnormalities. XPV shows normal nucleotide excision repair, but an exaggerated delay in recovery of replicative DNA synthesis. Most XPV patients do not develop clinical symptoms and skin neoplasias until a later age. Clinical manifestations are limited to photo-induced deterioration of the skin and eyes.<ref>PMID:10385124</ref> <ref>PMID:10398605</ref> <ref>PMID:11032022</ref> <ref>PMID:11121129</ref> <ref>PMID:11773631</ref> | ||
| + | == Function == | ||
| + | [[http://www.uniprot.org/uniprot/POLH_HUMAN POLH_HUMAN]] DNA polymerase specifically involved in DNA repair. Plays an important role in translesion synthesis, where the normal high fidelity DNA polymerases cannot proceed and DNA synthesis stalls. Plays an important role in the repair of UV-induced pyrimidine dimers. Depending on the context, it inserts the correct base, but causes frequent base transitions and transversions. May play a role in hypermutation at immunoglobulin genes. Forms a Schiff base with 5'-deoxyribose phosphate at abasic sites, but does not have lyase activity. Targets POLI to replication foci.<ref>PMID:10385124</ref> <ref>PMID:11743006</ref> <ref>PMID:11376341</ref> <ref>PMID:14630940</ref> <ref>PMID:14734526</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Cytarabine (AraC) is an essential chemotherapeutic for acute myeloid leukemia (AML) and resistance to this drug is a major cause of treatment failure. AraC is a nucleoside analog that differs from 2'-deoxycytidine only by the presence of an additional hydroxyl group at the C2' position of the 2'-deoxyribose. The active form of the drug AraC 5'-triphosphate (AraCTP) is utilized by human replicative DNA polymerases to insert AraC at the 3' terminus of a growing DNA chain. This impedes further primer extension and is a primary basis for the drug action. The Y-family translesion synthesis (TLS) DNA polymerase eta (Poleta) counteracts this barrier to DNA replication by efficient extension from AraC-terminated primers. Here, we provide high-resolution structures of human Poleta with AraC incorporated at the 3'-primer terminus. We show that Poleta can accommodate AraC at different stages of the catalytic cycle, and that it can manipulate the conformation of the AraC sugar via specific hydrogen bonding and stacking interactions. Taken together, the structures provide a basis for the ability of Poleta to extend DNA synthesis from AraC terminated primers. | ||
| - | + | Structural basis for polymerase eta-promoted resistance to the anticancer nucleoside analog cytarabine.,Rechkoblit O, Choudhury JR, Buku A, Prakash L, Prakash S, Aggarwal AK Sci Rep. 2018 Aug 23;8(1):12702. doi: 10.1038/s41598-018-30796-w. PMID:30140014<ref>PMID:30140014</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 6d0m" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: DNA-directed DNA polymerase]] | ||
| + | [[Category: Aggarwal, A K]] | ||
| + | [[Category: Rechkoblit, O]] | ||
| + | [[Category: Arac]] | ||
| + | [[Category: Cytarabine]] | ||
| + | [[Category: Dna damage]] | ||
| + | [[Category: Dna replication]] | ||
| + | [[Category: Dna synthesis]] | ||
| + | [[Category: Transferase]] | ||
| + | [[Category: Transferase-dna complex]] | ||
| + | [[Category: Translesion]] | ||
Revision as of 10:06, 5 September 2018
Polymerase Eta post-insertion binary complex with cytarabine (AraC)
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