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Title: SbnG, a citrate synthase in Staphylococcus aureus: A new fold on an old enzyme

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. In this paper, 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. Finally, 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:
 [1] ;  [1] ;  [2] ;  [2] ;  [1]
  1. Univ. of British Columbia, Vancouver, BC (Canada)
  2. Univ. of Western Ontario, London, ON (Canada)
Publication Date:
Grant/Contract Number:
P41RR001209; MOP-102596
Type:
Accepted Manuscript
Journal Name:
Journal of Biological Chemistry
Additional Journal Information:
Journal Volume: 289; Journal Issue: 49; Journal ID: ISSN 0021-9258
Publisher:
American Society for Biochemistry and Molecular Biology
Research Org:
Univ. of British Columbia, Vancouver, BC (Canada); Univ. of Western Ontario, London, ON (Canada)
Sponsoring Org:
USDOE Office of Science (SC), Biological and Environmental Research (BER) (SC-23); National Inst. of Health (NIH) (United States); Canadian Inst. of Health Research (CIHR) (Canada); Natural Sciences and Engineering Research Council of Canada (NSERC); National Research Council Canada; Province of Saskatchewan (Canada); Western Economic Diversification Canada; Univ. of Saskatchewan (Canada)
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; crystal structure; iron; siderophore; Staphylococcus aureus (S. aureus); tricarboxylic acid cycle (TCA Cycle) (Krebs Cycle); citrate synthase; convergent evolution
OSTI Identifier:
1349646

Kobylarz, Marek J., Grigg, Jason C., Sheldon, Jessica R., Heinrichs, David E., and Murphy, Michael E. P.. SbnG, a citrate synthase in Staphylococcus aureus: A new fold on an old enzyme. United States: N. p., Web. doi:10.1074/jbc.M114.603175.
Kobylarz, Marek J., Grigg, Jason C., Sheldon, Jessica R., Heinrichs, David E., & Murphy, Michael E. P.. SbnG, a citrate synthase in Staphylococcus aureus: A new fold on an old enzyme. United States. doi:10.1074/jbc.M114.603175.
Kobylarz, Marek J., Grigg, Jason C., Sheldon, Jessica R., Heinrichs, David E., and Murphy, Michael E. P.. 2014. "SbnG, a citrate synthase in Staphylococcus aureus: A new fold on an old enzyme". United States. doi:10.1074/jbc.M114.603175. https://www.osti.gov/servlets/purl/1349646.
@article{osti_1349646,
title = {SbnG, a citrate synthase in Staphylococcus aureus: A new fold on an old enzyme},
author = {Kobylarz, Marek J. and Grigg, Jason C. and Sheldon, Jessica R. and Heinrichs, David E. and Murphy, Michael E. P.},
abstractNote = {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. In this paper, 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. Finally, 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.},
doi = {10.1074/jbc.M114.603175},
journal = {Journal of Biological Chemistry},
number = 49,
volume = 289,
place = {United States},
year = {2014},
month = {10}
}