RGFGIGS is an amino acid sequence required for acetyl coenzyme A binding and activity of human spermidine/spermine N1acetyltransferase

Li Lu, Kimberly A. Berkey, Robert A. Casero

Research output: Contribution to journalArticlepeer-review

Abstract

Polyamine catabolism is rate limited by spermidine/spermine N1- acetyltransferase (SSAT). Although the amino acid sequence of SSAT is known, the substrate binding and catalytic sites are not. The goal of this study was to define the region responsible for acetyl coenzyme A binding. Human SSAT contains a region of 20 amino acids homologous to several microbial antibiotic N-acetyltransferases. The highest homology is represented in the Campylobacter coli streptothricin acetyltransferase sat4 gene, where 16 identical or highly conserved amino acids exist in a 20-residue stretch. The most conserved residues within this region are RGFGIGS beginning at Arg-101 in the human SSAT. Site-directed mutations to Arg-101, Gly-104, and Gly-106 resulted in proteins with no measurable activity. The G102D mutation produced a partially active protein with a decreased affinity for acetyl coenzyme A and with a K(m) >10-fold that of the wild-type protein. Analysis using the PredictProtein program suggests a common structure among the microbial and eukaryotic N-acetyltransferases in the region corresponding to the RGFGIGS of human SSAT consisting of an α-helix usually preceded by a glycine loop. Our data are consistent with the hypothesis that Arg-101 and the proximal glycine loop are necessary for the activity of human SSAT.

Original languageEnglish (US)
Pages (from-to)18920-18924
Number of pages5
JournalJournal of Biological Chemistry
Volume271
Issue number31
DOIs
StatePublished - 1996

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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