Structural characterization of cals8, a tdp-α-d-glucose dehydrogenase involved in calicheamicin aminodideoxypentose biosynthesis

Shanteri Singh, Karolina Michalska, Lance Bigelow, Michael Endres, Madan K. Kharel, Gyorgy Babnigg, Ragothaman M. Yennamalli, Craig A. Bingman, Andrzej Joachimiak, Jon S. Thorson, George N. Phillips

Research output: Contribution to journalArticlepeer-review

3 Scopus citations


Classical UDP-glucose 6-dehydrogenases (UGDHs; EC catalyze the conversion of UDP-α-D-glucose (UDPGlc) to the key metabolic precursor UDP-α-D-glucuronic acid (UDP-GlcA) and display specificity for UDP-Glc. The fundamental biochemical and structural study of the UGDH homolog CalS8 encoded by the calicheamicin biosynthetic gene is reported and represents one of the first studies of a UGDH homolog involved in secondary metabolism. The corresponding biochemical characterization of CalS8 reveals CalS8 as one of the first characterized base-permissive UGDH homologs with a >15-fold preference for TDP-Glc over UDP-Glc. The corresponding structure elucidations of apo-CalS8 and the CalS8· substrate·cofactor ternary complex (at 2.47 and 1.95 Å resolution, respectively) highlight a notably high degree of conservation between CalS8 and classical UGDHs where structural divergence within the intersubunit loop structure likely contributes to the CalS8 base permissivity. As such, this study begins to provide a putative blueprint for base specificity among sugar nucleotide-dependent dehydrogenases and, in conjunction with prior studies on the base specificity of the calicheamicin aminopentosyltransferase CalG4, provides growing support for the calicheamicin aminopentose pathway as a TDP-sugar-dependent process.

Original languageEnglish
Pages (from-to)26249-26258
Number of pages10
JournalJournal of Biological Chemistry
Issue number43
StatePublished - Oct 23 2015

Bibliographical note

Publisher Copyright:
© 2015 by The American Society for Biochemistry and Molecular Biology, Inc. Published in the U.S.A.

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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