2OXM

Crystal structure of a UNG2/modified DNA complex that represent a stabilized short-lived extrahelical state in ezymatic DNA base flipping

Summary for 2OXM

• Entry DOI: 10.2210/pdb2oxm/pdb
• Descriptor: DNA (5'-D(*TP*GP*TP*TP*AP*TP*CP*TP*T)-3'), DNA (5'-D(*AP*AP*AP*GP*AP*TP*(4MF)P*AP*CP*A)-3'), Uracil-DNA glycosylase, ... (4 entities in total)
• Functional Keywords: enzyme dna complex, ung2, uracil dna glycosylase, hydrolase-dna complex, hydrolase/dna
• Biological source: Homo sapiens (human); More
• Cellular location: Isoform 1: Mitochondrion. Isoform 2: Nucleus: P13051
• Total number of polymer chains: 3
• Total formula weight: 31322.05

Authors

Bianchet, M.A.,Krosky, D.J.,Stivers, J.T.,Amzel, L.M. (deposition date: 2007-02-20, release date: 2007-10-30, Last modification date: 2023-08-30)

Primary citation

Parker, J.B.,Bianchet, M.A.,Krosky, D.J.,Friedman, J.I.,Amzel, L.M.,Stivers, J.T.
Enzymatic capture of an extrahelical thymine in the search for uracil in DNA.
Nature, 449:433-437, 2007

PubMed Abstract: The enzyme uracil DNA glycosylase (UNG) excises unwanted uracil bases in the genome using an extrahelical base recognition mechanism. Efficient removal of uracil is essential for prevention of C-to-T transition mutations arising from cytosine deamination, cytotoxic U*A pairs arising from incorporation of dUTP in DNA, and for increasing immunoglobulin gene diversity during the acquired immune response. A central event in all of these UNG-mediated processes is the singling out of rare U*A or U*G base pairs in a background of approximately 10(9) T*A or C*G base pairs in the human genome. Here we establish for the human and Escherichia coli enzymes that discrimination of thymine and uracil is initiated by thermally induced opening of T*A and U*A base pairs and not by active participation of the enzyme. Thus, base-pair dynamics has a critical role in the genome-wide search for uracil, and may be involved in initial damage recognition by other DNA repair glycosylases.

PubMed: 17704764
DOI: 10.1038/nature06131

Experimental method

X-RAY DIFFRACTION (2.5 Å)