PDBsum entry 1xpu

Transcription/RNA

PDB id: 1xpu

Contents

Protein chains

(+ 0 more) 408 a.a. *

Ligands

__U-__C ×6

AGS ×6

FPD ×5

Metals

_MG ×6

Waters ×20

* Residue conservation analysis

PDB id:

1xpu

Name:

Transcription/RNA

Title:

Structural mechanism of inhibition of the rho transcription termination factor by the antibiotic 5a-(3-formylphenylsulfanyl)- dihydrobicyclomycin (fpdb)

Structure:

5'-r( Cp Up Cp Up Cp Up Cp U)-3'. Chain: g, m, h, j, k, l. Engineered: yes. Other_details: ssrna. Rho transcription termination factor. Chain: a, b, c, d, e, f. Engineered: yes

Source:

Synthetic: yes. Escherichia coli. Organism_taxid: 562. Expressed in: escherichia coli. Expression_system_taxid: 562.

Biol. unit:

24mer (from PQS)

Resolution:

3.05Å R-factor: 0.288 R-free: 0.295

Authors:

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

Key ref:

E.Skordalakes et al. (2005). Structural mechanism of inhibition of the Rho transcription termination factor by the antibiotic bicyclomycin. Structure, 13, 99. PubMed id: 15642265 DOI: 10.1016/j.str.2004.10.013

Date:

09-Oct-04 Release date: 02-Nov-04

Protein chains

P0AG30  (RHO_ECOLI) -  Transcription termination factor Rho from Escherichia coli (strain K12)

Seq: 419 a.a.

Struc: 408 a.a.

Enzyme reactions

• Enzyme class: E.C.3.6.4.- - ?????

DOI no: 10.1016/j.str.2004.10.013

Structure 13:99 (2005)

PubMed id: 15642265

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

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

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.

Selected figure(s)

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.

The above figure is reprinted by permission from Cell Press: Structure (2005, 13, 99-0) copyright 2005.

Figure was selected by an automated process.