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

Nicole Renee Pendini, Min Yin Yap, Daouda A K Traore, Steven W Polyak, Nathan Philip Cowieson, A D Abell, Grant William Booker, John Campbell Wallace, Jacqueline Anne Wilce, Matthew Charles James Wilce

Research output: Contribution to journalArticleResearchpeer-review

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.
Original languageEnglish
Pages (from-to)762 - 773
Number of pages12
JournalProtein Science
Volume22
Issue number6
DOIs
Publication statusPublished - 2013

Cite this

Pendini, Nicole Renee ; Yap, Min Yin ; Traore, Daouda A K ; Polyak, Steven W ; Cowieson, Nathan Philip ; Abell, A D ; Booker, Grant William ; Wallace, John Campbell ; Wilce, Jacqueline Anne ; Wilce, Matthew Charles James. / Structural characterization of Staphylococcus aureus biotin protein ligase and interaction partners: An antibiotic target. In: Protein Science. 2013 ; Vol. 22, No. 6. pp. 762 - 773.
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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-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.",
author = "Pendini, {Nicole Renee} and Yap, {Min Yin} and Traore, {Daouda A K} and Polyak, {Steven W} and Cowieson, {Nathan Philip} and Abell, {A D} and Booker, {Grant William} and Wallace, {John Campbell} and Wilce, {Jacqueline Anne} and Wilce, {Matthew Charles James}",
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pages = "762 -- 773",
journal = "Protein Science",
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Structural characterization of Staphylococcus aureus biotin protein ligase and interaction partners: An antibiotic target. / Pendini, Nicole Renee; Yap, Min Yin; Traore, Daouda A K; Polyak, Steven W; Cowieson, Nathan Philip; Abell, A D; Booker, Grant William; Wallace, John Campbell; Wilce, Jacqueline Anne; Wilce, Matthew Charles James.

In: Protein Science, Vol. 22, No. 6, 2013, p. 762 - 773.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Pendini, Nicole Renee

AU - Yap, Min Yin

AU - Traore, Daouda A K

AU - Polyak, Steven W

AU - Cowieson, Nathan Philip

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AU - Wallace, John Campbell

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AB - 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.

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