Intein-mediated rapid purification of recombinant human pituitary adenylate cyclase activating polypeptide

Acta Biochim Biophys Sin (Shanghai). 2004 Nov;36(11):759-66. doi: 10.1093/abbs/36.11.759.

Abstract

In order to obtain the recombinant human PACAP efficiently by intein-mediated single column purification, a gene encoding human PACAP was synthesized and cloned into Escherichia coli expression vector pKYB. The recombinant vector pKY-PAC was transferred into E. coli ER2566 cells and the target protein was over-expressed as a fusion to the N-terminus of a self-cleavable affinity tag. After the PACAP-intein-CBD fusion protein was purified by chitin-affinity chromatography, the self-cleavage activity of the intein was induced by DTT and the rhPACAP was released from the chitin-bound intein tag. The activity of the rhPACAP to stimulate cyclic AMP accumulation was detected using the human pancreas carcinoma cells SW1990. Twenty-two milligrams of rhPACAP with the purity over 98% was obtained by single column purification from 1 liter of induced culture. The preliminary biological assay indicated that the rhPACAP, which has an extra Met at its N-terminus compared with the native human PACAP, had the similar activity of stimulating cAMP accumulation with the standard PACAP38 in the SW1990 cells. A new efficient production procedure of the active recombinant human PACAP was established.

MeSH terms

  • Base Sequence
  • Biochemistry / methods*
  • Chitin / chemistry
  • Chromatography, Affinity
  • Dithiothreitol / chemistry
  • Electrophoresis, Polyacrylamide Gel
  • Escherichia coli / metabolism
  • Genetic Vectors
  • Humans
  • Inteins*
  • Lasers
  • Mass Spectrometry
  • Molecular Sequence Data
  • Nerve Growth Factors / chemistry*
  • Nerve Growth Factors / isolation & purification*
  • Neuropeptides / chemistry*
  • Neuropeptides / isolation & purification*
  • Neurotransmitter Agents / chemistry*
  • Neurotransmitter Agents / isolation & purification*
  • Peptides / chemistry
  • Pituitary Adenylate Cyclase-Activating Polypeptide
  • Plasmids / metabolism
  • Protein Binding
  • Protein Structure, Tertiary
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Proteins / chemistry
  • Sequence Analysis, DNA

Substances

  • ADCYAP1 protein, human
  • Nerve Growth Factors
  • Neuropeptides
  • Neurotransmitter Agents
  • Peptides
  • Pituitary Adenylate Cyclase-Activating Polypeptide
  • Recombinant Fusion Proteins
  • Recombinant Proteins
  • Chitin
  • Dithiothreitol