1ynn
From Proteopedia
(New page: 200px<br /><applet load="1ynn" size="450" color="white" frame="true" align="right" spinBox="true" caption="1ynn, resolution 3.30Å" /> '''Taq RNA polymerase-r...) |
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| - | [[Image:1ynn.gif|left|200px]]<br /><applet load="1ynn" size=" | + | [[Image:1ynn.gif|left|200px]]<br /><applet load="1ynn" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1ynn, resolution 3.30Å" /> | caption="1ynn, resolution 3.30Å" /> | ||
'''Taq RNA polymerase-rifampicin complex'''<br /> | '''Taq RNA polymerase-rifampicin complex'''<br /> | ||
==Overview== | ==Overview== | ||
| - | A combined structural, functional, and genetic approach was used to | + | A combined structural, functional, and genetic approach was used to investigate inhibition of bacterial RNA polymerase (RNAP) by sorangicin (Sor), a macrolide polyether antibiotic. Sor lacks chemical and structural similarity to the ansamycin rifampicin (Rif), an RNAP inhibitor widely used to treat tuberculosis. Nevertheless, structural analysis revealed Sor binds in the same RNAP beta subunit pocket as Rif, with almost complete overlap of RNAP binding determinants, and functional analysis revealed that both antibiotics inhibit transcription by directly blocking the path of the elongating transcript at a length of 2-3 nucleotides. Genetic analysis indicates that Rif binding is extremely sensitive to mutations expected to change the shape of the antibiotic binding pocket, while Sor is not. We suggest that conformational flexibility of Sor, in contrast to the rigid conformation of Rif, allows Sor to adapt to changes in the binding pocket. This has important implications for drug design against rapidly mutating targets. |
==About this Structure== | ==About this Structure== | ||
| - | 1YNN is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Thermus_aquaticus Thermus aquaticus] with ZN and RFP as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/DNA-directed_RNA_polymerase DNA-directed RNA polymerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.6 2.7.7.6] Full crystallographic information is available from [http:// | + | 1YNN is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Thermus_aquaticus Thermus aquaticus] with <scene name='pdbligand=ZN:'>ZN</scene> and <scene name='pdbligand=RFP:'>RFP</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/DNA-directed_RNA_polymerase DNA-directed RNA polymerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.6 2.7.7.6] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1YNN OCA]. |
==Reference== | ==Reference== | ||
| Line 14: | Line 14: | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
[[Category: Thermus aquaticus]] | [[Category: Thermus aquaticus]] | ||
| - | [[Category: Campbell, E | + | [[Category: Campbell, E A.]] |
| - | [[Category: Darst, S | + | [[Category: Darst, S A.]] |
[[Category: Irschik, H.]] | [[Category: Irschik, H.]] | ||
[[Category: Jansen, R.]] | [[Category: Jansen, R.]] | ||
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[[Category: transferase]] | [[Category: transferase]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:07:12 2008'' |
Revision as of 14:07, 21 February 2008
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Taq RNA polymerase-rifampicin complex
Overview
A combined structural, functional, and genetic approach was used to investigate inhibition of bacterial RNA polymerase (RNAP) by sorangicin (Sor), a macrolide polyether antibiotic. Sor lacks chemical and structural similarity to the ansamycin rifampicin (Rif), an RNAP inhibitor widely used to treat tuberculosis. Nevertheless, structural analysis revealed Sor binds in the same RNAP beta subunit pocket as Rif, with almost complete overlap of RNAP binding determinants, and functional analysis revealed that both antibiotics inhibit transcription by directly blocking the path of the elongating transcript at a length of 2-3 nucleotides. Genetic analysis indicates that Rif binding is extremely sensitive to mutations expected to change the shape of the antibiotic binding pocket, while Sor is not. We suggest that conformational flexibility of Sor, in contrast to the rigid conformation of Rif, allows Sor to adapt to changes in the binding pocket. This has important implications for drug design against rapidly mutating targets.
About this Structure
1YNN is a Protein complex structure of sequences from Thermus aquaticus with and as ligands. Active as DNA-directed RNA polymerase, with EC number 2.7.7.6 Full crystallographic information is available from OCA.
Reference
Structural, functional, and genetic analysis of sorangicin inhibition of bacterial RNA polymerase., Campbell EA, Pavlova O, Zenkin N, Leon F, Irschik H, Jansen R, Severinov K, Darst SA, EMBO J. 2005 Feb 23;24(4):674-82. Epub 2005 Feb 3. PMID:15692574
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