SNAP output for PDB entry 2flp [SNAP web server]

PDB-id

2flp; SNAP-derived features in text and JSON formats; DNAproDB

Class

replication-DNA

Method

X-ray (2.4 Å)

Summary

Binary complex of the catalytic core of human DNA polymerase iota with DNA (template g)

Reference

Nair DT, Johnson RE, Prakash L, Prakash S, Aggarwal AK (2006): "An incoming nucleotide imposes an anti to syn conformational change on the templating purine in the human DNA polymerase-iota active site." Structure, 14, 749-755. doi: 10.1016/j.str.2006.01.010.

Abstract

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.