2FLP: Binary Complex Of The Catalytic Core Of Human Dna Polymerase Iota With Dna (Template G)

Substrate-induced conformational change of the protein is the linchpin of enzymatic reactions. Replicative DNA polymerases, for example, convert from an open to a closed conformation in response to dNTP binding. Human DNA polymerase-iota (hPoliota), a member of the Y family of DNA polymerases, differs strikingly from other polymerases in its much higher proficiency and fidelity for nucleotide incorporation opposite template purines than opposite template pyrimidines. We present here a crystallographic analysis of hPoliota binary complexes, which together with the ternary complexes show that, contrary to replicative DNA polymerases, the DNA, and not the polymerase, undergoes the primary substrate-induced conformational change. The incoming dNTP "pushes" templates A and G from the anti to the syn conformation dictated by a rigid hPoliota active site. Together, the structures posit a mechanism for template selection wherein dNTP binding induces a conformational switch in template purines for productive Hoogsteen base pairing.
PDB ID: 2FLPDownload
MMDB ID: 74632
PDB Deposition Date: 2006/1/6
Updated in MMDB: 2012/11
Experimental Method:
x-ray diffraction
Resolution: 2.4  Å
Source Organism:
synthetic construct
Similar Structures:
Biological Unit for 2FLP: hexameric; determined by author
Molecular Components in 2FLP
Label Count Molecule
Proteins (2 molecules)
DNA Polymerase Iota(Gene symbol: POLI)
Molecule annotation
Nucleotides(2 molecules)
DNA Template Strand
Molecule annotation
DNA Primer Strand
Molecule annotation
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Citing MMDB