title: SbnG, a citrate synthase in Staphylococcus aureus: a new fold on an old enzyme.
abstract: In response to iron deprivation, Staphylococcus aureus produces staphyloferrin B, a citrate-containing siderophore that delivers iron back to the cell. This bacterium also possesses a second citrate synthase, SbnG, that is necessary for supplying citrate to the staphyloferrin B biosynthetic pathway. We present the structure of SbnG bound to the inhibitor calcium and an active site variant in complex with oxaloacetate. The overall fold of SbnG is structurally distinct from TCA cycle citrate synthases yet similar to metal-dependent class II aldolases. Phylogenetic analyses revealed that SbnG forms a separate clade with homologs from other siderophore biosynthetic gene clusters and is representative of a metal-independent subgroup in the phosphoenolpyruvate/pyruvate domain superfamily. A structural superposition of the SbnG active site to TCA cycle citrate synthases and site-directed mutagenesis suggests a case for convergent evolution toward a conserved catalytic mechanism for citrate production.
authors.affiliation: From the Department of Microbiology and Immunology, Life Sciences Institute, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada and.
authors.forename: Marek J
authors.initials: MJ
authors.lastname: Kobylarz
authors.affiliation: From the Department of Microbiology and Immunology, Life Sciences Institute, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada and.
authors.forename: Jason C
authors.initials: JC
authors.lastname: Grigg
authors.affiliation: the Department of Microbiology and Immunology and.
authors.forename: Jessica R
authors.initials: JR
authors.lastname: Sheldon
authors.affiliation: the Department of Microbiology and Immunology and the Centre for Human Immunology University of Western Ontario, London, Ontario N6A 5C1, Canada.
authors.forename: David E
authors.initials: DE
authors.lastname: Heinrichs
authors.affiliation: From the Department of Microbiology and Immunology, Life Sciences Institute, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada and Michael.Murphy@ubc.ca.
authors.forename: Michael E P
authors.initials: ME
authors.lastname: Murphy
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry* / Q000145:classification / Q000235:genetics / Q000378:metabolism; D002950:Citrate (si)-Synthase / Q000737:chemistry* / Q000145:classification / Q000235:genetics / Q000378:metabolism; D002951:Citrates / Q000096:biosynthesis; D002952:Citric Acid Cycle / Q000235:genetics; D018360:Crystallography, X-Ray; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D019143:Evolution, Molecular; D015870:Gene Expression; D007501:Iron / Q000378:metabolism*; D035925:Iron-Regulatory Proteins / Q000737:chemistry* / Q000145:classification / Q000235:genetics / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D062907:Oxaloacetic Acid / Q000378:metabolism; D010728:Phosphoenolpyruvate / Q000378:metabolism; D010802:Phylogeny; D017510:Protein Folding; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D019289:Pyruvic Acid / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000145:classification / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D013211:Staphylococcus aureus / Q000737:chemistry* / Q000201:enzymology
chemical_list: D001426:Bacterial Proteins; D002951:Citrates; D035925:Iron-Regulatory Proteins; D011994:Recombinant Proteins; C083439:staphyloferrin B; D062907:Oxaloacetic Acid; D010728:Phosphoenolpyruvate; D019289:Pyruvic Acid; D007501:Iron; D002950:Citrate (si)-Synthase
keywords: Citrate Synthase; Convergent Evolution; Crystal Structure; Iron; Siderophore; Staphylococcus aureus (S. aureus); Tricarboxylic Acid Cycle (TCA Cycle) (Krebs Cycle)