1xpr: Difference between revisions

Revision as of 16:57, 21 February 2008

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

OverviewOverview

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.

About this StructureAbout this Structure

1XPR is a Single protein structure of sequence from Escherichia coli with , and as ligands. Full crystallographic information is available from OCA.

ReferenceReference

Structural mechanism of inhibition of the Rho transcription termination factor by the antibiotic bicyclomycin., Skordalakes E, Brogan AP, Park BS, Kohn H, Berger JM, Structure. 2005 Jan;13(1):99-109. PMID:15642265

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-[[Image:1xpr.gif|left|200px]]<br /><applet load="1xpr" size="450" color="white" frame="true" align="right" spinBox="true"
+[[Image:1xpr.gif|left|200px]]<br /><applet load="1xpr" size="350" color="white" frame="true" align="right" spinBox="true"
 caption="1xpr, resolution 3.15&Aring;" />
 '''Structural mechanism of inhibition of the Rho transcription termination factor by the antibiotic 5a-formylbicyclomycin (FB)'''<br />
 ==Overview==
-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.
+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.
 ==About this Structure==
-XPR is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] with MG, AGS and FB as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1XPR OCA].
+XPR is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] with <scene name='pdbligand=MG:'>MG</scene>, <scene name='pdbligand=AGS:'>AGS</scene> and <scene name='pdbligand=FB:'>FB</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1XPR OCA].
 ==Reference==
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 [[Category: Escherichia coli]]
 [[Category: Single protein]]
-[[Category: Berger, J.M.]]
+[[Category: Berger, J M.]]
-[[Category: Brogan, A.P.]]
+[[Category: Brogan, A P.]]
 [[Category: Kohn, H.]]
-[[Category: Park, B.S.]]
+[[Category: Park, B S.]]
 [[Category: Skordalakes, E.]]
 [[Category: AGS]]
@@ Line 23: / Line 23: @@
 [[Category: rho; 5a-formylbicyclomycin; fb; atpgammas]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Wed Nov 21 06:15:11 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:57:23 2008''