4KLE

DNA polymerase beta matched reactant complex with Mg2+, 10 s

Summary for 4KLE

• Entry DOI: 10.2210/pdb4kle/pdb
• Related: 4KLD 4KLF 4KLG 4KLH 4KLI 4KLJ 4KLL 4KLM 4KLO 4KLP 4KLQ 4KLS 4KLT 4KLU
• Descriptor: 5'-D(*CP*CP*GP*AP*CP*GP*GP*CP*GP*CP*AP*TP*CP*AP*GP*C)-3', 5'-D(*GP*CP*TP*GP*AP*TP*GP*CP*GP*CP*C)-3'), 5'-D(P*GP*TP*CP*GP*G)-3', ... (8 entities in total)
• Functional Keywords: dna polymerase, transferase, lyase-dna complex, lyase/dna
• Biological source: Homo sapiens (human)
• Cellular location: Nucleus: P06746
• Total number of polymer chains: 4
• Total formula weight: 48690.79

Authors

Freudenthal, B.D.,Beard, W.A.,Shock, D.D.,Wilson, S.H. (deposition date: 2013-05-07, release date: 2013-07-17, Last modification date: 2023-09-20)

Primary citation

Freudenthal, B.D.,Beard, W.A.,Shock, D.D.,Wilson, S.H.
Observing a DNA polymerase choose right from wrong.
Cell(Cambridge,Mass.), 154:157-168, 2013

PubMed Abstract: DNA polymerase (pol) β is a model polymerase involved in gap-filling DNA synthesis utilizing two metals to facilitate nucleotidyl transfer. Previous structural studies have trapped catalytic intermediates by utilizing substrate analogs (dideoxy-terminated primer or nonhydrolysable incoming nucleotide). To identify additional intermediates during catalysis, we now employ natural substrates (correct and incorrect nucleotides) and follow product formation in real time with 15 different crystal structures. We are able to observe molecular adjustments at the active site that hasten correct nucleotide insertion and deter incorrect insertion not appreciated previously. A third metal binding site is transiently formed during correct, but not incorrect, nucleotide insertion. Additionally, long incubations indicate that pyrophosphate more easily dissociates after incorrect, compared to correct, nucleotide insertion. This appears to be coupled to subdomain repositioning that is required for catalytic activation/deactivation. The structures provide insights into a fundamental chemical reaction that impacts polymerase fidelity and genome stability.

PubMed: 23827680
DOI: 10.1016/j.cell.2013.05.048

Experimental method

X-RAY DIFFRACTION (1.97 Å)