2a6h
From Proteopedia
(New page: 200px<br /><applet load="2a6h" size="450" color="white" frame="true" align="right" spinBox="true" caption="2a6h, resolution 2.40Å" /> '''Crystal structure of...) |
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| - | [[Image:2a6h.gif|left|200px]]<br /><applet load="2a6h" size=" | + | [[Image:2a6h.gif|left|200px]]<br /><applet load="2a6h" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="2a6h, resolution 2.40Å" /> | caption="2a6h, resolution 2.40Å" /> | ||
'''Crystal structure of the T. thermophilus RNA polymerase holoenzyme in complex with antibiotic sterptolydigin'''<br /> | '''Crystal structure of the T. thermophilus RNA polymerase holoenzyme in complex with antibiotic sterptolydigin'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Streptolydigin (Stl) is a potent inhibitor of bacterial RNA polymerases | + | Streptolydigin (Stl) is a potent inhibitor of bacterial RNA polymerases (RNAPs). The 2.4 A resolution structure of the Thermus thermophilus RNAP-Stl complex showed that, in full agreement with the available genetic data, the inhibitor binding site is located 20 A away from the RNAP active site and encompasses the bridge helix and the trigger loop, two elements that are considered to be crucial for RNAP catalytic center function. Structure-based biochemical experiments revealed additional determinants of Stl binding and demonstrated that Stl does not affect NTP substrate binding, DNA translocation, and phosphodiester bond formation. The RNAP-Stl complex structure, its comparison with the closely related substrate bound eukaryotic transcription elongation complexes, and biochemical analysis suggest an inhibitory mechanism in which Stl stabilizes catalytically inactive (preinsertion) substrate bound transcription intermediate, thereby blocking structural isomerization of RNAP to an active configuration. The results provide a basis for a design of new antibiotics utilizing the Stl-like mechanism. |
==About this Structure== | ==About this Structure== | ||
| - | 2A6H is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Thermus_thermophilus Thermus thermophilus] with STD, ZN and MG 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:// | + | 2A6H is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Thermus_thermophilus Thermus thermophilus] with <scene name='pdbligand=STD:'>STD</scene>, <scene name='pdbligand=ZN:'>ZN</scene> and <scene name='pdbligand=MG:'>MG</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=2A6H OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Nikiforov, V.]] | [[Category: Nikiforov, V.]] | ||
[[Category: Perederina, A.]] | [[Category: Perederina, A.]] | ||
| - | [[Category: RSGI, RIKEN | + | [[Category: RSGI, RIKEN Structural Genomics/Proteomics Initiative.]] |
[[Category: Savkina, M.]] | [[Category: Savkina, M.]] | ||
[[Category: Severinov, K.]] | [[Category: Severinov, K.]] | ||
| - | [[Category: Tahirov, T | + | [[Category: Tahirov, T H.]] |
[[Category: Temiakov, D.]] | [[Category: Temiakov, D.]] | ||
| - | [[Category: Vassylyev, D | + | [[Category: Vassylyev, D G.]] |
| - | [[Category: Vassylyeva, M | + | [[Category: Vassylyeva, M N.]] |
[[Category: Wakatsuki, S.]] | [[Category: Wakatsuki, S.]] | ||
[[Category: Zenkin, N.]] | [[Category: Zenkin, N.]] | ||
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[[Category: transcription regulation]] | [[Category: transcription regulation]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:24:03 2008'' |
Revision as of 14:24, 21 February 2008
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Crystal structure of the T. thermophilus RNA polymerase holoenzyme in complex with antibiotic sterptolydigin
Overview
Streptolydigin (Stl) is a potent inhibitor of bacterial RNA polymerases (RNAPs). The 2.4 A resolution structure of the Thermus thermophilus RNAP-Stl complex showed that, in full agreement with the available genetic data, the inhibitor binding site is located 20 A away from the RNAP active site and encompasses the bridge helix and the trigger loop, two elements that are considered to be crucial for RNAP catalytic center function. Structure-based biochemical experiments revealed additional determinants of Stl binding and demonstrated that Stl does not affect NTP substrate binding, DNA translocation, and phosphodiester bond formation. The RNAP-Stl complex structure, its comparison with the closely related substrate bound eukaryotic transcription elongation complexes, and biochemical analysis suggest an inhibitory mechanism in which Stl stabilizes catalytically inactive (preinsertion) substrate bound transcription intermediate, thereby blocking structural isomerization of RNAP to an active configuration. The results provide a basis for a design of new antibiotics utilizing the Stl-like mechanism.
About this Structure
2A6H is a Protein complex structure of sequences from Thermus thermophilus 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 basis of transcription inhibition by antibiotic streptolydigin., Temiakov D, Zenkin N, Vassylyeva MN, Perederina A, Tahirov TH, Kashkina E, Savkina M, Zorov S, Nikiforov V, Igarashi N, Matsugaki N, Wakatsuki S, Severinov K, Vassylyev DG, Mol Cell. 2005 Sep 2;19(5):655-66. PMID:16167380
Page seeded by OCA on Thu Feb 21 16:24:03 2008
Categories: DNA-directed RNA polymerase | Protein complex | Thermus thermophilus | Igarashi, N. | Matsugaki, N. | Nikiforov, V. | Perederina, A. | RSGI, RIKEN Structural Genomics/Proteomics Initiative. | Savkina, M. | Severinov, K. | Tahirov, T H. | Temiakov, D. | Vassylyev, D G. | Vassylyeva, M N. | Wakatsuki, S. | Zenkin, N. | Zorov, S. | MG | STD | ZN | Antibiotic | Riken structural genomics/proteomics initiative | Rna polymerase holoenzyme | Rsgi | Streptolydigin | Structural genomics | Transcription regulation
