Development of a Selective Activity-Based Probe for Adenylating Enzymes: Profiling MbtA Involved in Siderophore Biosynthesis from <i>Mycobacterium tuberculosis</i>

Duckworth, Benjamin P.; Wilson, Daniel J.; Nelson, Kathryn M.; Boshoff, Helena I.; Barry, Clifton E.; Aldrich, Courtney C.

doi:10.1021/cb300112x

Cited by 54 publications

(62 citation statements)

References 27 publications

(71 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Several chemistry-based approaches have exploited selective chemical labeling of thioesterase (TE), 6 dehydratase (DH), 7 and aryl acid adenylating enzymes 8 found in any PKS and/or NRPS enzymes in bacterial proteomes. As not all domains are present in each PKS and NRPS enzymes, a more complete set of probes may be critical to identify full modules and realize practical proteomic approaches consisting of activity-based probes to natural product biosynthetic pathways.…”

mentioning

confidence: 99%

Active site-directed proteomic probes for adenylation domains in nonribosomal peptide synthetases

et al. 2015

View full text Add to dashboard Cite

Adenylation (A) domains found in all nonribosomal peptide synthetase (NRPS) modules are essential catalytic components and function as gatekeepers to select amino acid building blocks during nonribosomal peptide biosynthesis. Leveraging the strict substrate recognition characteristics of these enzymes, we targeted the development of active site-directed proteomic probes for A domains in NRPSs that enable detection, isolation, identification, and enzymatic characterization of A domains in native proteomes. Here, we describe a general strategy for selective chemical labeling of individual A domains in NRPS enzymes using active site-directed proteomic probes coupled to 5′-O-N-(aminoacyl)sulfamoyladenosine (AMS) scaffold with a clickable benzophenone functionality. These probes selectively target individual A domains in natural product producer proteomes by ligand-directed protein labeling. The data demonstrate that these proteomic tools can greatly facilitate the molecular identification, functional characterization, and profiling of virtually any kind of A domains of NRPS enzymes in complex biological systems.

show abstract

mentioning

confidence: 99%

Active site-directed proteomic probes for adenylation domains in nonribosomal peptide synthetases

et al. 2015

View full text Add to dashboard Cite

show abstract

“…The importance of the mycobacterial siderophore biosynthesis pathway has led to the development of a designed small-molecule inhibitor, salicyl-AMS [5=-O-(N-salicylsulfamoyl)adenosine] (see Fig. S1 in the supplemental material), that specifically targets MbtA by mimicking the salicyl-AMP intermediate (9)(10)(11). In vitro studies have confirmed that salicyl-AMS inhibits MbtA activity and also inhibits M. tuberculosis growth in iron-depleted media (9,12), with the MIC for M. tuberculosis H37Rv found to be 0.5 g/ml in a study with an alamarBlue assay (13).…”

mentioning

confidence: 99%

Pharmacokinetic and In Vivo Efficacy Studies of the Mycobactin Biosynthesis Inhibitor Salicyl-AMS in Mice

Lun

Guo

Adamson³

et al. 2013

Antimicrob Agents Chemother

View full text Add to dashboard Cite

“…The broth microdilution method (Duckworth et al, 2012), which in a survey (Franzblau et al, 2012), was found to be the mostly used protocol in the field, was employed for the preliminary screening. All extracts were screened against both M. tb.…”

Section: 0 Materials and Methodsmentioning

confidence: 99%

Some Nigerian anti-tuberculosis ethnomedicines: A preliminary efficacy assessment

Ibekwe¹,

Nvau²,

Oladosu³

et al. 2014

Journal of Ethnopharmacology

Self Cite

View full text Add to dashboard Cite

Ethnopharmacological significance Nigerian herbalists possess indigenous ethnomedicinal recipes for the management of tuberculosis and related ailments. Aim of the study To carry out a collaborative preliminary modern scientific evaluation of the efficacy of some Nigerian ethnomedicines used by traditional medicine practitioners (TMPs) in the management of tuberculosis and related ailments Materials and methods Ethnomedicinal recipes (ETMs) were collected from TMPs from locations in various ecological zones of Nigeria under a collaborative understanding. The aqueous methanolic extracts of the ETMs were screened against Mycobacterium bovis, BCG and Mycobacterium tuberculosis (M. tb.) strain H37Rv using the broth microdilution method. Results Extracts of ETMs screened against BCG showed 69% activity against the organism. The activities varied from weak, ≤ 2500μg /mL to highly active, 33μg /mL 64% of the extracts were active against M. tb. The activities of the extracts against M.tb. varied from weak, ≤ 2500μg /mL to highly active, 128μg/mL. There was 77% agreement in results obtained using BCG or M. tb. as test organisms Conclusion The results show clear evidence for the efficacy of the majority of indigenous Nigerian herbal recipes in the ethnomedicinal management of tuberculosis and related ailments. BCG may be effectively used, to a great extent, as the organism for screening for potential anti-M. tb. agents. A set of prioritization criteria for the selection of plants for initial further studies for the purpose of antituberculsis drug discovery research is proposed.

show abstract

Development of a Selective Activity-Based Probe for Adenylating Enzymes: Profiling MbtA Involved in Siderophore Biosynthesis from Mycobacterium tuberculosis

Cited by 54 publications

References 27 publications

Active site-directed proteomic probes for adenylation domains in nonribosomal peptide synthetases

Active site-directed proteomic probes for adenylation domains in nonribosomal peptide synthetases

Pharmacokinetic and In Vivo Efficacy Studies of the Mycobactin Biosynthesis Inhibitor Salicyl-AMS in Mice

Some Nigerian anti-tuberculosis ethnomedicines: A preliminary efficacy assessment

Contact Info

Product

Resources

About