Sulfonamide-Based Inhibitors of Biotin Protein Ligase as New Antibiotic Leads

2019 ◽  
Vol 14 (9) ◽  
pp. 1990-1997 ◽  
Author(s):  
Kwang Jun Lee ◽  
William Tieu ◽  
Beatriz Blanco-Rodriguez ◽  
Ashleigh S. Paparella ◽  
Jingxian Yu ◽  
...  
Keyword(s):  
Biotin Protein Ligase

A Division of labor between two biotin protein ligase homologs

2021 ◽  
Author(s):  
Xuejiao Song ◽  
Sarah K Henke ◽  
John E. Cronan
Keyword(s):  
Division Of Labor ◽  
Biotin Protein Ligase

Leishmania major biotin protein ligase forms a unique cross-handshake dimer

2021 ◽  
Vol 77 (4) ◽  
pp. 510-521
Author(s):  
Manoj Kumar Rajak ◽  
Sonika Bhatnagar ◽  
Shubhant Pandey ◽  
Sunil Kumar ◽  
Shalini Verma ◽  
...  
Keyword(s):  
Leishmania Major ◽  
Size Exclusion ◽  
Covalent Attachment ◽  
Mitochondrial Enzymes ◽  
Dependent Manner ◽  
Post Translational Modification ◽  
Terminal Domain ◽  
Exclusion Chromatography ◽  
Partial Unfolding ◽  
Biotin Protein Ligase

Biotin protein ligase catalyses the post-translational modification of biotin carboxyl carrier protein (BCCP) domains, a modification that is crucial for the function of several carboxylases. It is a two-step process that results in the covalent attachment of biotin to the ɛ-amino group of a conserved lysine of the BCCP domain of a carboxylase in an ATP-dependent manner. In Leishmania, three mitochondrial enzymes, acetyl-CoA carboxylase, methylcrotonyl-CoA carboxylase and propionyl-CoA carboxylase, depend on biotinylation for activity. In view of the indispensable role of the biotinylating enzyme in the activation of these carboxylases, crystal structures of L. major biotin protein ligase complexed with biotin and with biotinyl-5′-AMP have been solved. L. major biotin protein ligase crystallizes as a unique dimer formed by cross-handshake interactions of the hinge region of the two monomers formed by partial unfolding of the C-terminal domain. Interestingly, the substrate (BCCP domain)-binding site of each monomer is occupied by its own C-terminal domain in the dimer structure. This was observed in all of the crystals that were obtained, suggesting a closed/inactive conformation of the enzyme. Size-exclusion chromatography studies carried out using high protein concentrations (0.5 mM) suggest the formation of a concentration-dependent dimer that exists in equilibrium with the monomer.

Structure Guided Design of Biotin Protein Ligase Inhibitors for Antibiotic Discovery

2013 ◽  
Vol 14 (1) ◽  
pp. 4-20 ◽  
Author(s):  
Ashleigh Paparella ◽  
Tatiana Soares da Costa ◽  
Min Yap ◽  
William Tieu ◽  
Matthew Wilce ◽  
...  
Keyword(s):  
Biotin Protein Ligase ◽  
Antibiotic Discovery

scholarly journals Advanced Resistance Studies Identify Two Discrete Mechanisms in Staphylococcus aureus to Overcome Antibacterial Compounds that Target Biotin Protein Ligase

Antibiotics ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 165 ◽  
Author(s):  
Andrew J. Hayes ◽  
Jiulia Satiaputra ◽  
Louise M. Sternicki ◽  
Ashleigh S. Paparella ◽  
Zikai Feng ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Transcriptional Repression ◽  
Molecular Mechanisms ◽  
Resistance Mechanism ◽  
Resistance Mechanisms ◽  
Resistance Rate ◽  
Biotin Protein Ligase ◽  
Essential Enzyme

Biotin protein ligase (BPL) inhibitors are a novel class of antibacterial that target clinically important methicillin-resistant Staphylococcus aureus (S. aureus). In S. aureus, BPL is a bifunctional protein responsible for enzymatic biotinylation of two biotin-dependent enzymes, as well as serving as a transcriptional repressor that controls biotin synthesis and import. In this report, we investigate the mechanisms of action and resistance for a potent anti-BPL, an antibacterial compound, biotinyl-acylsulfamide adenosine (BASA). We show that BASA acts by both inhibiting the enzymatic activity of BPL in vitro, as well as functioning as a transcription co-repressor. A low spontaneous resistance rate was measured for the compound (<10−9) and whole-genome sequencing of strains evolved during serial passaging in the presence of BASA identified two discrete resistance mechanisms. In the first, deletion of the biotin-dependent enzyme pyruvate carboxylase is proposed to prioritize the utilization of bioavailable biotin for the essential enzyme acetyl-CoA carboxylase. In the second, a D200E missense mutation in BPL reduced DNA binding in vitro and transcriptional repression in vivo. We propose that this second resistance mechanism promotes bioavailability of biotin by derepressing its synthesis and import, such that free biotin may outcompete the inhibitor for binding BPL. This study provides new insights into the molecular mechanisms governing antibacterial activity and resistance of BPL inhibitors in S. aureus.

Biotin protein ligase from Corynebacterium glutamicum: role for growth and l-lysine production

2011 ◽  
Vol 93 (6) ◽  
pp. 2493-2502 ◽  
Author(s):  
P. Peters-Wendisch ◽  
K. C. Stansen ◽  
S. Götker ◽  
V. F. Wendisch
Keyword(s):  
Corynebacterium Glutamicum ◽  
Lysine Production ◽  
Biotin Protein Ligase

scholarly journals Purification, crystallization and preliminary crystallographic analysis of biotin protein ligase fromStaphylococcus aureus

2008 ◽  
Vol 64 (6) ◽  
pp. 520-523 ◽  
Author(s):  
Nicole R. Pendini ◽  
Steve W. Polyak ◽  
Grant W. Booker ◽  
John C. Wallace ◽  
Matthew C. J. Wilce
Keyword(s):  
Crystallographic Analysis ◽  
Biotin Protein Ligase

scholarly journals Protein: Protein Interactions in Control of the Escherichia Coli Biotin Protein Ligase Functional Switch

2013 ◽  
Vol 104 (2) ◽  
pp. 660a-661a
Author(s):  
Dorothy Beckett ◽  
Poorni Adikaram
Keyword(s):  
Escherichia Coli ◽  
Protein Interactions ◽  
Protein Protein Interactions ◽  
Biotin Protein Ligase

Biotin protein ligase from Candida albicans: Expression, purification and development of a novel assay

2008 ◽  
Vol 479 (2) ◽  
pp. 163-169 ◽  
Author(s):  
Nicole R. Pendini ◽  
Lisa M. Bailey ◽  
Grant W. Booker ◽  
Matthew C.J. Wilce ◽  
John C. Wallace ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Biotin Protein Ligase

scholarly journals Ligand Specificity of Group I Biotin Protein Ligase of Mycobacterium tuberculosis

PLoS ONE ◽  
2008 ◽  
Vol 3 (5) ◽  
pp. e2320 ◽  
Author(s):  
Sudha Purushothaman ◽  
Garima Gupta ◽  
Richa Srivastava ◽  
Vasanthakumar Ganga Ramu ◽  
Avadhesha Surolia
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Ligand Specificity ◽  
Group I ◽  
Biotin Protein Ligase

scholarly journals Promiscuous protein biotinylation by Escherichia coli biotin protein ligase

2008 ◽  
Vol 13 (11) ◽  
pp. 3043-3050 ◽  
Author(s):  
Eunjoo Choi-Rhee ◽  
Howard Schulman ◽  
John E. Cronan
Keyword(s):  
Escherichia Coli ◽  
Biotin Protein Ligase
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