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HIV1 integrase expressed in Escherichia coli from a synthetic gene.
Holler, T P; Foltin, S K; Ye, Q Z; Hupe, D J.
Afiliación
  • Holler TP; Department of Biochemistry, Parke-Davis Pharmaceutical Research, Division of Warner-Lambert Company, Ann Arbor, MI 48105.
Gene ; 136(1-2): 323-8, 1993 Dec 22.
Article en En | MEDLINE | ID: mdl-7916726
Human immunodeficiency virus type 1 (HIV1) integrase is cleaved from the gag-pol precursor by the HIV1 protease. The resulting 32-kDa protein is used by the infecting virus to insert a linear, double-stranded DNA copy of its genome, prepared by reverse transcription of viral RNA, into the host cell's chromosomal DNA. In order to achieve high levels of expression, to minimize an internal initiation problem and to facilitate mutagenesis, we have designed and synthesized a gene encoding the integrase from the infectious molecular clone, pNL4-3. Codon usage was optimized for expression in Escherichia coli and unique restriction sites were incorporated throughout the gene. A 905-bp cassette containing a ribosome-binding site, a start codon and the integrase-coding sequence, sandwiched between EcoRI and HindIII sites, was synthesized by overlap extension of nine long synthetic oligodeoxyribonucleotides [90-120 nucleotides (nt)] and subsequent amplification using two primers (28-30 nt). The cassette was subcloned into the vector pKK223-3 for expression under control of a tac promoter. The protein produced from this highly expressed gene has the expected N-terminal sequence and molecular mass, and displays the DNA processing, DNA joining and disintegration activities expected from recombinant integrase. These studies have demonstrated the utility of codon optimization, and lay the groundwork for structure-function studies of HIV1 integrase.
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: VIH-1 / ADN Nucleotidiltransferasas / Genes Sintéticos Idioma: En Revista: Gene Año: 1993 Tipo del documento: Article Pais de publicación: Países Bajos
Buscar en Google
Colección: 01-internacional Base de datos: MEDLINE Asunto principal: VIH-1 / ADN Nucleotidiltransferasas / Genes Sintéticos Idioma: En Revista: Gene Año: 1993 Tipo del documento: Article Pais de publicación: Países Bajos