Structural Basis for the Stereochemical Control of Amine Installation in Nucleotide Sugar Aminotransferases

Fengbin Wang, Shanteri Singh, Weijun Xu, Kate E. Helmich, Mitchell D. Miller, Hongnan Cao, Craig A. Bingman, Jon S. Thorson, George N. Phillips

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

Sugar aminotransferases (SATs) are an important class of tailoring enzymes that catalyze the 5′-pyridoxal phosphate (PLP)-dependent stereo- and regiospecific installation of an amino group from an amino acid donor (typically l-Glu or l-Gln) to a corresponding ketosugar nucleotide acceptor. Herein we report the strategic structural study of two homologous C4 SATs (Micromonospora echinospora CalS13 and Escherichia coli WecE) that utilize identical substrates but differ in their stereochemistry of aminotransfer. This study reveals for the first time a new mode of SAT sugar nucleotide binding and, in conjunction with previously reported SAT structural studies, provides the basis from which to propose a universal model for SAT stereo- and regiochemical control of amine installation. Specifically, the universal model put forth highlights catalytic divergence to derive solely from distinctions within nucleotide sugar orientation upon binding within a relatively fixed SAT active site where the available ligand bound structures of the three out of four representative C3 and C4 SAT examples provide a basis for the overall model. Importantly, this study presents a new predictive model to support SAT functional annotation, biochemical study and rational engineering.

Original languageEnglish
Pages (from-to)2048-2056
Number of pages9
JournalACS Chemical Biology
Volume10
Issue number9
DOIs
StatePublished - Sep 18 2015

Bibliographical note

Publisher Copyright:
© 2015 American Chemical Society.

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine

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