Conferring RNA polymerase activity to a DNA polymerase

A single residue in reverse transcriptase controls substrate selection

Guangxia Gao, Marianna Orlova, Millie Georgiadis, Wayne A. Hendrickson, Stephen P. Goff

Research output: Contribution to journalArticle

146 Citations (Scopus)

Abstract

The traditional classification of nucleic acid polymerases as either DNA or RNA polymerases is based, in large part, on their fundamental preference for the incorporation of either deoxyribonucleotides or ribonucleotides during chain elongation. The refined structure determination of Moloney murine leukemia virus reverse transcriptase, a strict DNA polymerase, recently allowed the prediction that a single amino acid residue at the active site might be responsible for the discrimination against the 2'OH group of an incoming ribonucleotide. Mutation of this residue resulted in a variant enzyme now capable of acting as an RNA polymerase. In marked contrast to the wild-type enzyme, the K(m) of the mutant enzyme for ribonucleotides was comparable to that for deoxyribonucleotides. The results are consistent with proposals of a common evolutionary origin for both classes of enzymes and support models of a common mechanism of nucleic acid synthesis underlying catalysis by all such polymerases.

Original languageEnglish (US)
Pages (from-to)407-411
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume94
Issue number2
DOIs
StatePublished - Jan 21 1997
Externally publishedYes

Fingerprint

RNA-Directed DNA Polymerase
DNA-Directed RNA Polymerases
Ribonucleotides
Deoxyribonucleotides
DNA-Directed DNA Polymerase
Enzymes
Nucleic Acids
Moloney murine leukemia virus
Catalysis
Catalytic Domain
Amino Acids
Mutation
DNA polymerase A

Keywords

  • deoxyribonucleotides
  • DNA synthesis

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Conferring RNA polymerase activity to a DNA polymerase : A single residue in reverse transcriptase controls substrate selection. / Gao, Guangxia; Orlova, Marianna; Georgiadis, Millie; Hendrickson, Wayne A.; Goff, Stephen P.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 94, No. 2, 21.01.1997, p. 407-411.

Research output: Contribution to journalArticle

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