3nae | pdb_00003nae

RB69 DNA Polymerase (Y567A) Ternary Complex with dATP Opposite Guanidinohydantoin

spinqualitylabelsall models 3nae, resolution 2.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3nae is a 3 chain structure with sequence from Enterobacteria phage rb69. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: CA, DTP NonStd Res: DOC, G35 Related: 3l8b, 3lzi, 3lzj, 2ozs, 1ig9 Gene: 43, gp43 (Enterobacteria phage RB69) Activity: DNA-directed DNA polymerase, with EC number 2.7.7.7 Resources: FirstGlance, OCA, RCSB, PDBsum Function [DPOL_BPR69] This polymerase possesses two enzymatic activities: DNA synthesis (polymerase) and an exonucleolytic activity that degrades single stranded DNA in the 3'- to 5'-direction. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed Continuous oxidative damage inflicted on DNA produces 7,8-dihydro-8-oxoguanine (8-oxoG), a commonly occurring lesion that can potentially cause cancer by producing G --> T transversions during DNA replication. Mild oxidation of 8-oxoG leads to the formation of hydantoins, specifically guanidinohydantoin (Gh) and spiroiminodihydantoin (Sp), which are 100% mutagenic because they encode almost exclusively the insertion of dAMP and dGMP (encoding G --> T and G --> C transversions, respectively). The wild-type (wt) pol alpha family DNA polymerase from bacteriophage RB69 (RB69pol) inserts dAMP and dGMP with low efficiency when situated opposite Gh. In contrast, the RB69pol Y567A mutant inserts both of these dNMPs opposite Gh with >100-fold higher efficiency than wt. We now report the crystal structure of the "closed" preinsertion complex for the Y567A mutant with dATP opposite a templating Gh (R-configuration) in a 13/18mer primer-template (P/T) at 2.0 A resolution. The structure data reveal that the Y to A substitution provides the nascent base pair binding pocket (NBP) with the flexibility to accommodate Gh by allowing G568 to move in the major-to-minor groove direction of the P/T. Thus, Gh is rejected as a templating base by wt RB69pol because G568 is inflexible, preventing Gh from pairing with the incoming dATP or dGTP base. Substitution of Ala for Tyr567 in RB69 DNA Polymerase Allows dAMP and dGMP To Be Inserted opposite Guanidinohydantoin .,Beckman J, Wang M, Blaha G, Wang J, Konigsberg WH Biochemistry. 2010 Sep 9. PMID:20795733 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also DNA polymerase

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