title: The structure of the carboxyltransferase component of acetyl-coA carboxylase reveals a zinc-binding motif unique to the bacterial enzyme.
abstract: Acetyl-coA carboxylase (ACC) is a central metabolic enzyme that catalyzes the committed step in fatty acid biosynthesis: biotin-dependent conversion of acetyl-coA to malonyl-coA. The bacterial carboxyltransferase (CT) subunit of ACC is a target for the design of novel therapeutics that combat severe, hospital-acquired infections resistant to the established classes of frontline antimicrobials. Here, we present the structures of the bacterial CT subunits from two prevalent nosocomial pathogens, Staphylococcus aureus and Escherichia coli, at a resolution of 2.0 and 3.0 A, respectively. Both structures reveal a small, independent zinc-binding domain that lacks a complement in the primary sequence or structure of the eukaryotic homologue.
authors.affiliation: Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA.
authors.forename: Patrick
authors.initials: P
authors.lastname: Bilder
authors.forename: Sandra
authors.initials: S
authors.lastname: Lightle
authors.forename: Graeme
authors.initials: G
authors.lastname: Bainbridge
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Ohren
authors.forename: Barry
authors.initials: B
authors.lastname: Finzel
authors.forename: Fang
authors.initials: F
authors.lastname: Sun
authors.forename: Susan
authors.initials: S
authors.lastname: Holley
authors.forename: Loola
authors.initials: L
authors.lastname: Al-Kassim
authors.forename: Cindy
authors.initials: C
authors.lastname: Spessard
authors.forename: Michael
authors.initials: M
authors.lastname: Melnick
authors.forename: Marcia
authors.initials: M
authors.lastname: Newcomer
authors.forename: Grover L
authors.initials: GL
authors.lastname: Waldrop
mesh_terms: D000103:Acetyl-CoA Carboxylase / Q000378:metabolism*; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D001419:Bacteria / Q000201:enzymology*; D001665:Binding Sites; D019878:Carboxyl and Carbamoyl Transferases / Q000378:metabolism*; D003428:Cross Infection / Q000201:enzymology; D018360:Crystallography, X-Ray; D004926:Escherichia coli / Q000201:enzymology; D005057:Eukaryotic Cells / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017510:Protein Folding; D013211:Staphylococcus aureus / Q000201:enzymology; D015032:Zinc / Q000378:metabolism*
chemical_list: D019878:Carboxyl and Carbamoyl Transferases; D000103:Acetyl-CoA Carboxylase; D015032:Zinc