What question did this study set out to answer?

Determine the structural determinants and mechanism by which fidaxomicin binds and inhibits Mycobacterium tuberculosis RNA polymerase.

February 26, 2018eLifeOpen Access

Fidaxomicin jams Mycobacterium tuberculosis RNA polymerase motions needed for initiation via RbpA contacts

View Full Paper

Ask AI

Bookmark

Determine the structural determinants and mechanism by which fidaxomicin binds and inhibits Mycobacterium tuberculosis RNA polymerase.
Determined the 3.4 Å resolution cryo-electron microscopy structure of a complete Mycobacterium tuberculosis RNA polymerase holoenzyme in complex with fidaxomicin.
Resolved intermediate conformational states of the enzyme spanning from the free apo-holoenzyme to the promoter-engaged open complex ready for transcription.
Identified direct structural contacts between the actinobacterial general transcription factor RbpA and fidaxomicin, explaining the drug's high potency against M. tuberculosis.
Demonstrated that fidaxomicin functions as a molecular doorstop, locking the polymerase in an open conformation and mechanically hindering the structural rearrangements required to secure promoter DNA in the active site.

Discussion

No takes yet. Share an insight, caveat, or question.

Implication

Cryo-electron microscopy study reveals fidaxomicin arrests Mycobacterium tuberculosis RNA polymerase via RbpA contacts, highlighting a template for targeted anti-tuberculosis drug design.

Cite This Study

Boyaci et al. (2018) studied this question.

synapsesocial.com/papers/6a9252c54913c8e05db882bc https://doi.org/10.7554/elife.34823

View Full Paper

Ask AI

Bookmark

Implication

Cryo-electron microscopy study reveals fidaxomicin arrests Mycobacterium tuberculosis RNA polymerase via RbpA contacts, highlighting a template for targeted anti-tuberculosis drug design.

Fidaxomicin jams Mycobacterium tuberculosis RNA polymerase motions needed for initiation via RbpA contacts

Key Points

Discussion

Implication

Cite This Study

Fidaxomicin jams Mycobacterium tuberculosis RNA polymerase motions needed for initiation via RbpA contacts

Key Points

Discussion

Implication

Cite This Study

Also Consider

Also Consider