Structural characterization of AtmS13, a putative sugar aminotransferase involved in indolocarbazole AT2433 aminopentose biosynthesis

Proteins. 2015 Aug;83(8):1547-54. doi: 10.1002/prot.24844. Epub 2015 Jul 1.

Abstract

AT2433 from Actinomadura melliaura is an indolocarbazole antitumor antibiotic structurally distinguished by its unique aminodideoxypentose-containing disaccharide moiety. The corresponding sugar nucleotide-based biosynthetic pathway for this unusual sugar derives from comparative genomics where AtmS13 has been suggested as the contributing sugar aminotransferase (SAT). Determination of the AtmS13 X-ray structure at 1.50-Å resolution reveals it as a member of the aspartate aminotransferase fold type I (AAT-I). Structural comparisons of AtmS13 with homologous SATs that act upon similar substrates implicate potential active site residues that contribute to distinctions in sugar C5 (hexose vs. pentose) and/or sugar C2 (deoxy vs. hydroxyl) substrate specificity.

Keywords: X-ray crystallography; carbohydrate; indolocarbazole; natural product; sugar nucleotide; transamination.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Actinomycetales / enzymology
  • Actinomycetales / genetics
  • Bacterial Proteins / chemistry*
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • Binding Sites
  • Carbazoles / metabolism*
  • Crystallography, X-Ray
  • Models, Molecular
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Transaminases / chemistry*
  • Transaminases / genetics
  • Transaminases / metabolism*

Substances

  • Bacterial Proteins
  • Carbazoles
  • Recombinant Proteins
  • Transaminases