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

Shanteri Singh, Youngchang Kim, Fengbin Wang, Lance Bigelow, Michael Endres, Madan K Kharel, Gyorgy Babnigg, Craig A Bingman, Andrzej Joachimiak, Jon S Thorson, George N Phillips

Index: Proteins 83 , 1547-54, (2015)

Full Text: HTML

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.© 2015 Wiley Periodicals, Inc.