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.
journal_name
ACS Chem Bioljournal_title
ACS chemical biologyauthors
Wang F,Singh S,Xu W,Helmich KE,Miller MD,Cao H,Bingman CA,Thorson JS,Phillips GN Jrdoi
10.1021/acschembio.5b00244subject
Has Abstractpub_date
2015-09-18 00:00:00pages
2048-56issue
9eissn
1554-8929issn
1554-8937journal_volume
10pub_type
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