Tagetitoxin inhibits RNA polymerase through trapping of the trigger loop.
J Biol Chem
; 286(46): 40395-400, 2011 Nov 18.
Article
in En
| MEDLINE
| ID: mdl-21976682
ABSTRACT
Tagetitoxin (Tgt) inhibits multisubunit chloroplast, bacterial, and some eukaryotic RNA polymerases (RNAPs). A crystallographic structure of Tgt bound to bacterial RNAP apoenzyme shows that Tgt binds near the active site but does not explain why Tgt acts only at certain sites. To understand the Tgt mechanism, we constructed a structural model of Tgt bound to the transcription elongation complex. In this model, Tgt interacts with the ß' subunit trigger loop (TL), stabilizing it in an inactive conformation. We show that (i) substitutions of the Arg residue of TL contacted by Tgt confer resistance to inhibitor; (ii) Tgt inhibits RNAP translocation, which requires TL movements; and (iii) paused complexes and a "slow" enzyme, in which the TL likely folds into an altered conformation, are resistant to Tgt. Our studies highlight the role of TL as a target through which accessory proteins and antibiotics can alter the elongation complex dynamics.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Organophosphorus Compounds
/
Bacterial Proteins
/
DNA-Directed RNA Polymerases
/
Models, Molecular
/
Thermus thermophilus
/
Dicarboxylic Acids
Language:
En
Journal:
J Biol Chem
Year:
2011
Type:
Article
Affiliation country:
United States