3PML
crystal structure of a polymerase lambda variant with a dGTP analog opposite a templating T
Summary for 3PML
Entry DOI | 10.2210/pdb3pml/pdb |
Related | 3GMH 3GMI 3PMH 3PMN 3PNC |
Descriptor | DNA polymerase lambda, 5'-D(*CP*GP*GP*CP*TP*GP*TP*AP*CP*TP*G)-3', 5'-D(P*GP*CP*CP*G)-3', ... (8 entities in total) |
Functional Keywords | protein-dna complex, lyase, transferase, dna, transferase-dna complex, transferase/dna |
Biological source | Homo sapiens (human) |
Cellular location | Nucleus : Q9UGP5 |
Total number of polymer chains | 8 |
Total formula weight | 87349.15 |
Authors | Bebenek, K.,Pedersen, L.C.,Kunkel, T.A. (deposition date: 2010-11-17, release date: 2011-01-26, Last modification date: 2024-11-20) |
Primary citation | Bebenek, K.,Pedersen, L.C.,Kunkel, T.A. Replication infidelity via a mismatch with Watson-Crick geometry. Proc.Natl.Acad.Sci.USA, 108:1862-1867, 2011 Cited by PubMed Abstract: In describing the DNA double helix, Watson and Crick suggested that "spontaneous mutation may be due to a base occasionally occurring in one of its less likely tautomeric forms." Indeed, among many mispairing possibilities, either tautomerization or ionization of bases might allow a DNA polymerase to insert a mismatch with correct Watson-Crick geometry. However, despite substantial progress in understanding the structural basis of error prevention during polymerization, no DNA polymerase has yet been shown to form a natural base-base mismatch with Watson-Crick-like geometry. Here we provide such evidence, in the form of a crystal structure of a human DNA polymerase λ variant poised to misinsert dGTP opposite a template T. All atoms needed for catalysis are present at the active site and in positions that overlay with those for a correct base pair. The mismatch has Watson-Crick geometry consistent with a tautomeric or ionized base pair, with the pH dependence of misinsertion consistent with the latter. The results support the original idea that a base substitution can originate from a mismatch having Watson-Crick geometry, and they suggest a common catalytic mechanism for inserting a correct and an incorrect nucleotide. A second structure indicates that after misinsertion, the now primer-terminal G • T mismatch is also poised for catalysis but in the wobble conformation seen in other studies, indicating the dynamic nature of the pathway required to create a mismatch in fully duplex DNA. PubMed: 21233421DOI: 10.1073/pnas.1012825108 PDB entries with the same primary citation |
Experimental method | X-RAY DIFFRACTION (2.6 Å) |
Structure validation
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