4ru9
From Proteopedia
(Difference between revisions)
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| - | ''' | + | ==Crystal structure of human DNA polymerase eta inserting dCMPNPP opposite a MeFapy-dG adducted DNA template== |
| + | <StructureSection load='4ru9' size='340' side='right' caption='[[4ru9]], [[Resolution|resolution]] 2.65Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[4ru9]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4RU9 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4RU9 FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0KX:2-DEOXY-5-O-[(R)-HYDROXY{[(R)-HYDROXY(PHOSPHONOOXY)PHOSPHORYL]AMINO}PHOSPHORYL]CYTIDINE'>0KX</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr> | ||
| + | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MF7:N-{2-AMINO-5-[FORMYL(METHYL)AMINO]-6-HYDROXYPYRIMIDIN-4-YL}-2-DEOXY-5-O-PHOSPHONO-BETA-D-ERYTHRO-PENTOFURANOSYLAMINE'>MF7</scene></td></tr> | ||
| + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4rua|4rua]]</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=4ru9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ru9 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4ru9 RCSB], [http://www.ebi.ac.uk/pdbsum/4ru9 PDBsum]</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 == | ||
| + | N(6)-(2-Deoxy-d-erythro-pentofuranosyl)-2,6-diamino-3,4-dihydro-4-oxo-5-N-methylf ormamidopyrimidine (MeFapy-dG) arises from N7-methylation of deoxyguanosine followed by imidazole ring opening. The lesion has been reported to persist in animal tissues. Previous in vitro replication bypass investigations of the MeFapy-dG adduct revealed predominant insertion of C opposite the lesion, dependent on the identity of the DNA polymerase (Pol) and the local sequence context. Here we report crystal structures of ternary Pol.DNA.dNTP complexes between MeFapy-dG-adducted DNA template:primer duplexes and the Y-family polymerases human Pol eta and P2 Pol IV (Dpo4) from Sulfolobus solfataricus. The structures of the hPol eta and Dpo4 complexes at the insertion and extension stages, respectively, are representative of error-free replication, with MeFapy-dG in the anti conformation and forming Watson-Crick pairs with dCTP or dC. | ||
| - | + | Structural Basis for Error-Free Bypass of the 5-N-Methylformamidopyrimidine-dG Lesion by Human DNA Polymerase eta and Sulfolobus solfataricus P2 Polymerase IV.,Patra A, Banerjee S, Johnson Salyard TL, Malik CK, Christov PP, Rizzo CJ, Stone MP, Egli M J Am Chem Soc. 2015 Jun 10;137(22):7011-4. doi: 10.1021/jacs.5b02701. Epub 2015, May 27. PMID:25988947<ref>PMID:25988947</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| - | + | == References == | |
| - | [[Category: | + | <references/> |
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: DNA-directed DNA polymerase]] | ||
[[Category: Egli, M]] | [[Category: Egli, M]] | ||
[[Category: Patra, A]] | [[Category: Patra, A]] | ||
| + | [[Category: Cytidine triphosphate]] | ||
| + | [[Category: Dna binding]] | ||
| + | [[Category: Dna damage]] | ||
| + | [[Category: Dna-directed dna polymerase]] | ||
| + | [[Category: Mefapy-dg lesion bypass]] | ||
| + | [[Category: Transferase-dna complex]] | ||
| + | [[Category: Y-family polymerase]] | ||
Revision as of 20:01, 5 August 2015
Crystal structure of human DNA polymerase eta inserting dCMPNPP opposite a MeFapy-dG adducted DNA template
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