4LVS: DNA polymerase beta mismatched substrate complex with Mn2+, 2.5 min

DNA polymerase (pol) beta 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.
PDB ID: 4LVSDownload
MMDB ID: 113274
PDB Deposition Date: 2013/7/26
Updated in MMDB: 2017/11
Experimental Method:
x-ray diffraction
Resolution: 2.002  Å
Source Organism:
Homo sapiens
Similar Structures:
Biological Unit for 4LVS: tetrameric; determined by author and by software (PISA)
Molecular Components in 4LVS
Label Count Molecule
Protein (1 molecule)
DNA Polymerase Beta(Gene symbol: POLB)
Molecule annotation
Nucleotides(3 molecules)
DNA (5'-d(p*gp*tp*cp*gp*g)-3')
Molecule annotation
DNA (5'-d(*gp*cp*tp*gp*ap*tp*gp*cp*gp*c)-3')
Molecule annotation
DNA (5'-d(*cp*cp*gp*ap*cp*gp*gp*cp*gp*cp*ap*tp*cp*ap*gp*c)-3')
Molecule annotation
Chemicals (9 molecules)
* Click molecule labels to explore molecular sequence information.

Citing MMDB