Structural characterization of Staphylococcus aureus biotin protein ligase and interaction partners: An antibiotic target

Date

2013

Authors

Pendini, N.
Yap, M.
Polyak, S.
Cowieson, N.
Abell, A.
Booker, G.
Wallace, J.
Wilce, J.
Wilce, M.

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Journal article

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Protein Science, 2013; 22(6):762-773

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Nicole R. Pendini, Min Y. Yap, Steven W. Polyak, Nathan P. Cowieson, Andrew Abell, Grant W. Booker, John C. Wallace, Jacqueline A. Wilce, and Matthew C. J. Wilce

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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-50-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.

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Corrected by: Erratum: Structural characterisation of Staphylococcus aureus biotin protein ligase and interaction partners: An antibiotic target, in Vol. 23, Issue 1, 121. Daouda Traore, was inadvertently omitted from the published version of their manuscript. Data source: Supporting information, https://doi.org/10.1002/pro.2262

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© 2013 The Protein Society

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