The covalent attachment of a phosphopantetheinyl (4'-PP) arm to a variety of synthases and other proteins is a key posttranslational protein modification. The 4'-PP is installed on the proteins post-translationally from coenzyme A (CoA) on a conserved serine residue by action of phosphopantetheinyl transferase (PPTase) enzymes. Phosphopantetheinylation is essential for synthase activity, and more ..
Target
Depositor Specified Assays
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| AID | Name | Type | Comment |
|---|---|---|---|
| 1490 | qHTS Assay for Inhibitors of Bacillus subtilis Sfp phosphopantetheinyl transferase (PPTase) | confirmatory | |
| 624112 | qHTS Assay for Inhibitors of Bacillus subtilis Sfp phosphopantetheinyl transferase (PPTase): Aqueous Solubility in PBS | other | |
| 624119 | qHTS Assay for Inhibitors of Bacillus subtilis Sfp phosphopantetheinyl transferase (PPTase): CYP 2D6 | other | |
| 2701 | Confirmation qHTS Assay for Inhibitors of Bacillus subtilis Sfp phosphopantetheinyl transferase (PPTase) | confirmatory | |
| 540352 | qHTS for Inhibitos of Bacillus subtilis Sfp phosphopantetheinyl transferase (PPTase): Chemistry Optimization Followup in B. Subtilis 168 | confirmatory | |
| 602480 | qHTS Assay for Inhibitors of Bacillus subtilis Sfp phosphopantetheinyl transferase (PPTase): Aqueous Solubility in PBS | other | |
| 602373 | qHTS Assay for Inhibitors of Bacillus subtilis Sfp phosphopantetheinyl transferase (PPTase): Hepg2 Assay | confirmatory | |
| 493214 | Inhibitos of Bacillus subtilis Sfp phosphopantetheinyl transferase (PPTase): Dry Powder Followup | confirmatory | |
| 540350 | qHTS Assay for Inhibitos of Bacillus subtilis Sfp phosphopantetheinyl transferase (PPTase): Chemistry Optimization Followup | confirmatory | |
| 602360 | qHTS Assay for Inhibitors of Bacillus subtilis AcpS phosphopantetheinyl transferase (PPTase): SAR | confirmatory | |
| 602366 | qHTS Assay for Inhibitors of Bacillus subtilis Sfp phosphopantetheinyl transferase (PPTase): SAR in B subtilis HM489 | confirmatory | |
| 602392 | qHTS Assay for Inhibitors of Bacillus subtilis Sfp phosphopantetheinyl transferase (PPTase): Label Free Assay for SAR | other | |
| 602479 | qHTS Assay for Inhibitors of Bacillus subtilis Sfp phosphopantetheinyl transferase (PPTase): Mouse Liver Microsome Stability (Half Time) | other | |
| 2707 | Gel-Based Assay for Inhibitors of Bacillus subtilis Sfp phosphopantetheinyl transferase (PPTase) | confirmatory | |
| 540353 | qHTS for Inhibitos of Bacillus subtilis Sfp phosphopantetheinyl transferase (PPTase): Chemistry Optimization Followup in B. Subtilis HM489 | confirmatory | |
| 540355 | Gel-Based Assay for Inhibitos of Bacillus subtilis Sfp phosphopantetheinyl transferase (PPTase): Chemistry Optimization Followup | confirmatory | |
| 602362 | qHTS Assay for Inhibitors of Bacillus subtilis Sfp phosphopantetheinyl transferase (PPTase): Gel Based Assay | confirmatory | |
| 602391 | qHTS Assay for Inhibitors of Bacillus subtilis Sfp phosphopantetheinyl transferase (PPTase): SAR in hGST A1-1 | confirmatory | |
| 624113 | qHTS Assay for Inhibitors of Bacillus subtilis Sfp phosphopantetheinyl transferase (PPTase): Mouse Plasma Stability | other | |
| 602371 | qHTS Assay for Inhibitors of Bacillus subtilis Sfp phosphopantetheinyl transferase (PPTase): SAR in B subtilis 168 | confirmatory | |
| 624118 | qHTS Assay for Inhibitors of Bacillus subtilis Sfp phosphopantetheinyl transferase (PPTase): CYP 3A4 | other | |
| 602370 | qHTS Assay for Inhibitors of Bacillus subtilis Sfp phosphopantetheinyl transferase (PPTase): SAR Round 2 | confirmatory |
Description:
Source: NIH Chemical Genomics Center [NCGC]
Assay Submitter: Michael Burkart, University of California, San Diego
Screening Center PI: Christopher P. Austin, NIH
Probe Development: NIH Chemical Genomics Center [NCGC]
NIH Grant Number: MH083266-01
The covalent attachment of a phosphopantetheinyl (4'-PP) arm to a variety of synthases and other proteins is a key posttranslational protein modification. The 4'-PP is installed on the proteins post-translationally from coenzyme A (CoA) on a conserved serine residue by action of phosphopantetheinyl transferase (PPTase) enzymes. Phosphopantetheinylation is essential for synthase activity, and removal of the PPTase gene precludes natural product synthesis in microorganisms, or in the case of fatty acid biosynthesis, renders the organism unviable. PPTase enzymes belong to a distinct structural superfamily. Within bacteria, these enzymes are grouped into two classes based upon primary structure, the AcpS-Type and Sfp-Type PPTases.
Sfp-type PPTases, corresponding to an activator of surfactin production in Bacillus subtilis, are responsible for modifying type I polyketide and nonribosomal peptide synthases of prokaryotes. Sfp-type PPTases are responsible for the activation of a variety of pathogen-associated virulence factors. Among these compounds are toxins such as mycolactone from Mycobacterium ulcerans, siderophores such as vibriobactin from Vibrio cholerae or mycobactin from Mycobacterium tuberculosis, as well as the mycolic acids which form the waxy cell wall of Mycobacteria. The biosyntheses of these natural products are considered attractive targets for drug design.
This BioAssay summarizes the development of novel small molecule Sfp-PPTase inhibitors and their follow-up characterization.
Assay Submitter: Michael Burkart, University of California, San Diego
Screening Center PI: Christopher P. Austin, NIH
Probe Development: NIH Chemical Genomics Center [NCGC]
NIH Grant Number: MH083266-01
The covalent attachment of a phosphopantetheinyl (4'-PP) arm to a variety of synthases and other proteins is a key posttranslational protein modification. The 4'-PP is installed on the proteins post-translationally from coenzyme A (CoA) on a conserved serine residue by action of phosphopantetheinyl transferase (PPTase) enzymes. Phosphopantetheinylation is essential for synthase activity, and removal of the PPTase gene precludes natural product synthesis in microorganisms, or in the case of fatty acid biosynthesis, renders the organism unviable. PPTase enzymes belong to a distinct structural superfamily. Within bacteria, these enzymes are grouped into two classes based upon primary structure, the AcpS-Type and Sfp-Type PPTases.
Sfp-type PPTases, corresponding to an activator of surfactin production in Bacillus subtilis, are responsible for modifying type I polyketide and nonribosomal peptide synthases of prokaryotes. Sfp-type PPTases are responsible for the activation of a variety of pathogen-associated virulence factors. Among these compounds are toxins such as mycolactone from Mycobacterium ulcerans, siderophores such as vibriobactin from Vibrio cholerae or mycobactin from Mycobacterium tuberculosis, as well as the mycolic acids which form the waxy cell wall of Mycobacteria. The biosyntheses of these natural products are considered attractive targets for drug design.
This BioAssay summarizes the development of novel small molecule Sfp-PPTase inhibitors and their follow-up characterization.
Protocol
Please see related BioAssays for all protocols relevant to this probe development project: AIDs 1490
Comment
Related BioAssays:
AID 1490: This assays is a validation of a quantitative high throughput screening (qHTS) protocol tested against 1,113 samples.
This summary assay will be updated as additional screens are run and small molecule probes have been developed.
AID 1490: This assays is a validation of a quantitative high throughput screening (qHTS) protocol tested against 1,113 samples.
This summary assay will be updated as additional screens are run and small molecule probes have been developed.
Additional Information
Grant Number: MH083266-01
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