title: Structural characterization of AtmS13, a putative sugar aminotransferase involved in indolocarbazole AT2433 aminopentose biosynthesis.
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.
authors.affiliation: Center for Pharmaceutical Research and Innovation, Pharmaceutical Sciences Division, University of Kentucky College of Pharmacy, Lexington, Kentucky, 40536-0596.
authors.forename: Shanteri
authors.initials: S
authors.lastname: Singh
authors.affiliation: Midwest Center for Structural Genomics and Structural Biology Center, Biosciences Division, Argonne National Laboratory, Argonne, Illinois, 60439.
authors.forename: Youngchang
authors.initials: Y
authors.lastname: Kim
authors.affiliation: Department of BioSciences, Rice University, Houston, Texas, 77005.
authors.forename: Fengbin
authors.initials: F
authors.lastname: Wang
authors.affiliation: Midwest Center for Structural Genomics and Structural Biology Center, Biosciences Division, Argonne National Laboratory, Argonne, Illinois, 60439.
authors.forename: Lance
authors.initials: L
authors.lastname: Bigelow
authors.affiliation: Midwest Center for Structural Genomics and Structural Biology Center, Biosciences Division, Argonne National Laboratory, Argonne, Illinois, 60439.
authors.forename: Michael
authors.initials: M
authors.lastname: Endres
authors.affiliation: School of Pharmacy, Department of Pharmaceutical Sciences, University of Maryland Eastern Shore, Princess Anne, Maryland.
authors.forename: Madan K
authors.initials: MK
authors.lastname: Kharel
authors.affiliation: Midwest Center for Structural Genomics and Structural Biology Center, Biosciences Division, Argonne National Laboratory, Argonne, Illinois, 60439.
authors.forename: Gyorgy
authors.initials: G
authors.lastname: Babnigg
authors.affiliation: Department of Biochemistry, University of Wisconsin-Madison, Madison, Wisconsin, 53706.
authors.forename: Craig A
authors.initials: CA
authors.lastname: Bingman
authors.affiliation: Midwest Center for Structural Genomics and Structural Biology Center, Biosciences Division, Argonne National Laboratory, Argonne, Illinois, 60439.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Joachimiak
authors.affiliation: Center for Pharmaceutical Research and Innovation, Pharmaceutical Sciences Division, University of Kentucky College of Pharmacy, Lexington, Kentucky, 40536-0596.
authors.forename: Jon S
authors.initials: JS
authors.lastname: Thorson
authors.affiliation: Department of BioSciences, Rice University, Houston, Texas, 77005.|Department of Biochemistry, University of Wisconsin-Madison, Madison, Wisconsin, 53706.|Department of Chemistry, Rice University, Houston, Texas, 77005.
authors.forename: George N
authors.initials: GN
authors.lastname: Phillips
mesh_terms: D000192:Actinomycetales / Q000201:enzymology / Q000235:genetics; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D001665:Binding Sites; D002227:Carbazoles / Q000378:metabolism*; D018360:Crystallography, X-Ray; D008958:Models, Molecular; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D000637:Transaminases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D002227:Carbazoles; D011994:Recombinant Proteins; D000637:Transaminases
keywords: X-ray crystallography; carbohydrate; indolocarbazole; natural product; sugar nucleotide; transamination