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Literature summary for 2.7.7.6 extracted from

  • Lilic, M.; Chen, J.; Boyaci, H.; Braffman, N.; Hubin, E.A.; Herrmann, J.; Mueller, R.; Mooney, R.; Landick, R.; Darst, S.A.; Campbell, E.A.
    The antibiotic sorangicin A inhibits promoter DNA unwinding in a Mycobacterium tuberculosis rifampicin-resistant RNA polymerase (2020), Proc. Natl. Acad. Sci. USA, 117, 30423-30432 .
    View publication on PubMedView publication on EuropePMC

Cloned(Commentary)

Cloned (Comment) Organism
-
Mycobacterium tuberculosis
-
Mycolicibacterium smegmatis

Crystallization (Commentary)

Crystallization (Comment) Organism
hanging drop vapor diffusion Mycobacterium tuberculosis
hanging drop vapor diffusion Mycolicibacterium smegmatis

Inhibitors

Inhibitors Comment Organism Structure
rifampicin
-
Mycobacterium tuberculosis
rifampicin
-
Mycolicibacterium smegmatis
sorangicin A inhibits the wild-type and mutant (S447/S456L) RNA polymerase through different mechanisms. It has a better pharmacokinetic profile than rifampicin, making it a suitable starting molecule to design drugs to be used for the treatment of tuberculosis patients with comorbidities who require multiple medications Mycobacterium tuberculosis
sorangicin A inhibits the wild-type and mutant (S447/S456L) RNA polymerase through different mechanisms. It has a better pharmacokinetic profile than rifampicin, making it a suitable starting molecule to design drugs to be used for the treatment of tuberculosis patients with comorbidities who require multiple medications; the inhibitor binds in the Rif-binding pocket of RNA. It inhibits inhibits the wild-type enzyme (RNAP) by a similar mechanism as rifampicin by preventing the translocation of very short RNAs. It inhibits the RifR S456L enzyme at an earlier step, preventing the transition of a partially unwound promoter DNA intermediate to the fully opened DNA and blocking the template-strand DNA from reaching the active site in the RNAP catalytic center Mycolicibacterium smegmatis

Organism

Organism UniProt Comment Textmining
Mycobacterium tuberculosis P9WGY9 AND P9WGY7 AND P9WGZ1 AND P9WGY5 AND P9WGI1 P9WGY9: subunit beta, P9WGY7: subunit beta', P9WGZ1: subunit alpha, P9WGY5: omega subunit, P9WGI1: sigma factor SigA, the RNAP catalytic core consists of 2 alpha, 1 beta, 1 beta' and 1 omega subunit. When a sigma factor is associated with the core the holoenzyme is formed, which can initiate transcription
-
Mycobacterium tuberculosis ATCC 25618 P9WGY9 AND P9WGY7 AND P9WGZ1 AND P9WGY5 AND P9WGI1 P9WGY9: subunit beta, P9WGY7: subunit beta', P9WGZ1: subunit alpha, P9WGY5: omega subunit, P9WGI1: sigma factor SigA, the RNAP catalytic core consists of 2 alpha, 1 beta, 1 beta' and 1 omega subunit. When a sigma factor is associated with the core the holoenzyme is formed, which can initiate transcription
-
Mycolicibacterium smegmatis A0QSL8 AND P60281 AND A0QS66 AND A0QWT1 A0QSL8: rpoA, subunit alpha, P60281: rpoB, subunit beta, A0QS66: rpoC, subunit beta', A0QWT1: rpoZ, subunit omega
-
Mycolicibacterium smegmatis P60281 AND A0QS66 AND A0QSL8 AND A0QWT1 AND A0QW02 P60281: beta subunit, A0QS66: beta' subunit, A0QSL8: alpha subunit, A0QWT1: omega subunit, A0QW02: sigma factor The RNAP catalytic core consists of 2 alpha, 1 beta, 1 beta' and 1 omega subunit. When a sigma factor is associated with the core the holoenzyme is formed, which can initiate transcription
-
Mycolicibacterium smegmatis ATCC 700084 A0QSL8 AND P60281 AND A0QS66 AND A0QWT1 A0QSL8: rpoA, subunit alpha, P60281: rpoB, subunit beta, A0QS66: rpoC, subunit beta', A0QWT1: rpoZ, subunit omega
-
Mycolicibacterium smegmatis ATCC 700084 P60281 AND A0QS66 AND A0QSL8 AND A0QWT1 AND A0QW02 P60281: beta subunit, A0QS66: beta' subunit, A0QSL8: alpha subunit, A0QWT1: omega subunit, A0QW02: sigma factor The RNAP catalytic core consists of 2 alpha, 1 beta, 1 beta' and 1 omega subunit. When a sigma factor is associated with the core the holoenzyme is formed, which can initiate transcription
-

Purification (Commentary)

Purification (Comment) Organism
-
Mycobacterium tuberculosis
-
Mycolicibacterium smegmatis

Synonyms

Synonyms Comment Organism
rifampicin-resistant RNA polymerase
-
Mycolicibacterium smegmatis
RNAP
-
Mycolicibacterium smegmatis

IC50 Value

IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
0.000005
-
pH 7.9, 37°C Mycolicibacterium smegmatis sorangicin A
0.000008
-
pH 7.9, 37°C Mycolicibacterium smegmatis rifampicin
0.00001
-
pH 7.9, 37°C Mycobacterium tuberculosis rifampicin
0.000033
-
pH 7.9, 37°C Mycobacterium tuberculosis sorangicin A
0.005
-
pH and temperature not specified in the publication Mycolicibacterium smegmatis rifampicin
0.008
-
pH and temperature not specified in the publication Mycolicibacterium smegmatis sorangicin A

General Information

General Information Comment Organism
drug target sorangicin A inhibits the wild-type and mutant RNA polymerase through different mechanisms. It has a better pharmacokinetic profile than rifampicin, making it a suitable starting molecule to design drugs to be used for the treatment of tuberculosis patients with comorbidities who require multiple medications Mycobacterium tuberculosis
drug target sorangicin A inhibits the wild-type and mutant RNA polymerase through different mechanisms. It has a better pharmacokinetic profile than rifampicin, making it a suitable starting molecule to design drugs to be used for the treatment of tuberculosis patients with comorbidities who require multiple medications Mycolicibacterium smegmatis