An Incoming Nucleotide Imposes an anti to syn Conformational Change on the Templating Purine in the Human DNA Polymerase-ι Active Site

Deepak T. Nair, Robert E. Johnson, Louise Prakash, Satya Prakash, Aneel K. Aggarwal

Research output: Contribution to journalArticle

46 Citations (Scopus)

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-ι (hPolι), 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 hPolι 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 hPolι 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.

Original languageEnglish (US)
Pages (from-to)749-755
Number of pages7
JournalStructure
Volume14
Issue number4
DOIs
StatePublished - Apr 2006

Fingerprint

DNA-Directed DNA Polymerase
Catalytic Domain
Nucleotides
Purines
Pyrimidines
purine
Base Pairing
Proteins

Keywords

  • DNA

ASJC Scopus subject areas

  • Molecular Biology
  • Structural Biology

Cite this

An Incoming Nucleotide Imposes an anti to syn Conformational Change on the Templating Purine in the Human DNA Polymerase-ι Active Site. / Nair, Deepak T.; Johnson, Robert E.; Prakash, Louise; Prakash, Satya; Aggarwal, Aneel K.

In: Structure, Vol. 14, No. 4, 04.2006, p. 749-755.

Research output: Contribution to journalArticle

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