title: Structural characterization of Staphylococcus aureus biotin protein ligase and interaction partners: an antibiotic target.
abstract: The essential metabolic enzyme biotin protein ligase (BPL) is a potential target for the development of new antibiotics required to combat drug-resistant pathogens. Staphylococcus aureus BPL (SaBPL) is a bifunctional protein, possessing both biotin ligase and transcription repressor activities. This positions BPL as a key regulator of several important metabolic pathways. Here, we report the structural analysis of both holo- and apo-forms of SaBPL using X-ray crystallography. We also present small-angle X-ray scattering data of SaBPL in complex with its biotin-carboxyl carrier protein substrate as well as the SaBPL:DNA complex that underlies repression. This has revealed the molecular basis of ligand (biotinyl-5'-AMP) binding and conformational changes associated with catalysis and repressor function. These data provide new information to better understand the bifunctional activities of SaBPL and to inform future strategies for antibiotic discovery.
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Victoria, Australia.
authors.forename: Nicole R
authors.initials: NR
authors.lastname: Pendini
authors.forename: Min Y
authors.initials: MY
authors.lastname: Yap
authors.forename: D A K
authors.initials: DA
authors.lastname: Traore
authors.forename: Steven W
authors.initials: SW
authors.lastname: Polyak
authors.forename: Nathan P
authors.initials: NP
authors.lastname: Cowieson
authors.forename: Andrew
authors.initials: A
authors.lastname: Abell
authors.forename: Grant W
authors.initials: GW
authors.lastname: Booker
authors.forename: John C
authors.initials: JC
authors.lastname: Wallace
authors.forename: Jacqueline A
authors.initials: JA
authors.lastname: Wilce
authors.forename: Matthew C J
authors.initials: MC
authors.lastname: Wilce
mesh_terms: D000103:Acetyl-CoA Carboxylase / Q000378:metabolism; D000249:Adenosine Monophosphate / Q000031:analogs & derivatives / Q000378:metabolism; D000595:Amino Acid Sequence; D001710:Biotin / Q000031:analogs & derivatives / Q000378:metabolism*; D019731:Carbon-Nitrogen Ligases / Q000737:chemistry* / Q000378:metabolism*; D018360:Crystallography, X-Ray; D054889:Fatty Acid Synthase, Type II / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D060066:Protein Interaction Maps; D055503:Protein Multimerization; D016415:Sequence Alignment; D013203:Staphylococcal Infections / Q000188:drug therapy / Q000382:microbiology; D013211:Staphylococcus aureus / Q000737:chemistry / Q000201:enzymology* / Q000378:metabolism
chemical_list: C082099:5'-AMP-biotin; D000249:Adenosine Monophosphate; D001710:Biotin; D054889:Fatty Acid Synthase, Type II; D019731:Carbon-Nitrogen Ligases; D000103:Acetyl-CoA Carboxylase; C079633:biotin carboxyl carrier protein
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