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Structural characterization of Staphylococcus aureus biotin protein ligase and interaction partners: An antibiotic target
Author(s) -
Pendini Nicole R.,
Yap Min Y.,
Polyak Steven W.,
Cowieson Nathan P.,
Abell Andrew,
Booker Grant W.,
Wallace John C.,
Wilce Jacqueline A.,
Wilce Matthew C. J.
Publication year - 2013
Publication title -
protein science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.353
H-Index - 175
eISSN - 1469-896X
pISSN - 0961-8368
DOI - 10.1002/pro.2262
Subject(s) - dna ligase , repressor , biochemistry , transcription (linguistics) , biotin , bifunctional , chemistry , biology , regulator , ligand (biochemistry) , dna , drug discovery , computational biology , transcription factor , gene , linguistics , philosophy , receptor , catalysis
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 ( Sa BPL) 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 Sa BPL using X‐ray crystallography. We also present small‐angle X‐ray scattering data of Sa BPL in complex with its biotin‐carboxyl carrier protein substrate as well as the Sa BPL: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 Sa BPL and to inform future strategies for antibiotic discovery.