1MQ3

Human DNA Polymerase Beta Complexed With Gapped DNA Containing an 8-oxo-7,8-dihydro-Guanine Template Paired with dCTP

Summary for 1MQ3

• Entry DOI: 10.2210/pdb1mq3/pdb
• Related: 1BPX 1BPY 1MQ2
• Descriptor: 5'-D(*CP*CP*GP*AP*CP*(8OG)P*GP*CP*GP*CP*AP*TP*CP*AP*GP*C)-3', 5'-D(*GP*CP*TP*GP*AP*TP*GP*CP*GP*(DOC))-3', 5'-D(P*GP*TP*CP*GP*G)-3', ... (8 entities in total)
• Functional Keywords: transferase, dna, transferase-dna complex, transferase/dna
• Biological source: Homo sapiens (human)
• Cellular location: Nucleus: P06746
• Total number of polymer chains: 4
• Total formula weight: 48245.31

Authors

Krahn, J.M.,Beard, W.A.,Miller, H.,Grollman, A.P.,Wilson, S.H. (deposition date: 2002-09-13, release date: 2003-01-28, Last modification date: 2024-02-14)

Primary citation

Krahn, J.M.,Beard, W.A.,Miller, H.,Grollman, A.P.,Wilson, S.H.
Structure of DNA Polymerase beta with the Mutagenic DNA Lesion 8-oxodeoxyguanine Reveals Structural Insights into its Coding Potential
Structure, 11:121-127, 2003

PubMed Abstract: Oxidative damage to DNA generates 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG). During DNA replication and repair synthesis, 8-oxodG can pair with cytosine or adenine. The ability to accurately replicate through this lesion depends on the DNA polymerase. We report the first structure of a polymerase with a promutagenic DNA lesion, 8-oxodG, in the confines of its active site. The modified guanine residue is in an anti conformation and forms Watson-Crick hydrogen bonds with an incoming dCTP. To accommodate the oxygen at C8, the 5'-phosphate backbone of the templating nucleotide flips 180 degrees. Thus, the flexibility of the template sugar-phosphate backbone near the polymerase active site is one parameter that influences the anti-syn equilibrium of 8-oxodG. Our results provide insights into the mechanisms employed by polymerases to select the complementary dNTP.

PubMed: 12517346
DOI: 10.1016/S0969-2126(02)00930-9

Experimental method

X-RAY DIFFRACTION (2.8 Å)