1XPR

Structural mechanism of inhibition of the Rho transcription termination factor by the antibiotic 5a-formylbicyclomycin (FB)

Summary for 1XPR

• Entry DOI: 10.2210/pdb1xpr/pdb
• Related: 1XPO 1XPU
• Descriptor: 5'-R(*CP*UP*CP*UP*CP*UP*CP*U)-3', Rho transcription termination factor, MAGNESIUM ION, ... (5 entities in total)
• Functional Keywords: rho; 5a-formylbicyclomycin; fb; atpgammas, transcription-rna complex, transcription/rna
• Biological source: Escherichia coli
• Total number of polymer chains: 12
• Total formula weight: 301760.37

Authors

Skordalakes, E.,Brogan, A.P.,Park, B.S.,Kohn, H.,Berger, J.M. (deposition date: 2004-10-09, release date: 2004-11-02, Last modification date: 2024-02-14)

Primary citation

Skordalakes, E.,Brogan, A.P.,Park, B.S.,Kohn, H.,Berger, J.M.
Structural mechanism of inhibition of the rho transcription termination factor by the antibiotic bicyclomycin
Structure, 13:99-109, 2005

PubMed Abstract: Rho is a hexameric RNA/DNA helicase/translocase that terminates transcription of select genes in bacteria. The naturally occurring antibiotic, bicyclomycin (BCM), acts as a noncompetitive inhibitor of ATP turnover to disrupt this process. We have determined three independent X-ray crystal structures of Rho complexed with BCM and two semisynthetic derivatives, 5a-(3-formylphenylsulfanyl)-dihydrobicyclomycin (FPDB) and 5a-formylbicyclomycin (FB) to 3.15, 3.05, and 3.15 A resolution, respectively. The structures show that BCM and its derivatives are nonnucleotide inhibitors that interact with Rho at a pocket adjacent to the ATP and RNA binding sites in the C-terminal half of the protein. BCM association prevents ATP turnover by an unexpected mechanism, occluding the binding of the nucleophilic water molecule required for ATP hydrolysis. Our data explain why only certain elements of BCM have been amenable to modification and serve as a template for the design of new inhibitors.

PubMed: 15642265
DOI: 10.1016/j.str.2004.10.013

Experimental method

X-RAY DIFFRACTION (3.15 Å)