PDBsum entry 1xpr

Transcription/RNA

PDB id

1xpr

Contents

			Protein chains

					(+ 0 more) 408 a.a.

			Ligands

					__U-__C ×6


					AGS ×6


					_FB ×5

			Metals

					_MG ×6

References listed in PDB file

Key reference

Title

Structural mechanism of inhibition of the rho transcription termination factor by the antibiotic bicyclomycin.

Authors

E.Skordalakes, A.P.Brogan, B.S.Park, H.Kohn, J.M.Berger.

Ref.

Structure, 2005, 13, 99. [DOI no: 10.1016/j.str.2004.10.013]

PubMed id

15642265

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.



	Figure 4. Figure 4. Rho-BCM Contacts (A) Stereo view of BCM (colored stick) bound to Rho. Amino acids involved in coordinating BCM are shown as gray sticks (Table 3). Mg2+ and ATPgS are shown as a magenta sphere and as black sticks. (B) Schematic of Rho-BCM contacts. Protein residues are colored black. BCM is shown in green. The additional contacts between the protein and the aldehyde groups of FPDB (yellow) and FB (blue) at the C(5a)-position of the [4.2.2] piperazinedione ring are also shown.

PROCHECK

	Headers