4kmu

From Proteopedia

(Difference between revisions)

Revision as of 22:23, 25 December 2014

X-ray crystal structure of the Escherichia coli RNA polymerase in complex with Rifampin

Structural highlights

4kmu is a 12 chain structure with sequence from Escherichia coli. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, ,
Related:	4kn4, 4kn7
Gene:	rpoA (Escherichia coli), rpoB (Escherichia coli), rpoC (Escherichia coli), rpoZ (Escherichia coli), rpoD (Escherichia coli)
Activity:	DNA-directed RNA polymerase, with EC number 2.7.7.6
Resources:	FirstGlance, OCA, RCSB, PDBsum

Function

[RPOZ_ECOLI] Promotes RNA polymerase assembly. Latches the N- and C-terminal regions of the beta' subunit thereby facilitating its interaction with the beta and alpha subunits.[HAMAP-Rule:MF_00366] [RPOA_ECOLI] DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. This subunit plays an important role in subunit assembly since its dimerization is the first step in the sequential assembly of subunits to form the holoenzyme.[HAMAP-Rule:MF_00059] [RPOC_ECOLI] DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates.[HAMAP-Rule:MF_01322] [RPOB_ECOLI] DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates.[HAMAP-Rule:MF_01321] [RPOD_ECOLI] Sigma factors are initiation factors that promote the attachment of RNA polymerase to specific initiation sites and are then released. This is the primary sigma factor of this bacterium.

Publication Abstract from PubMed

Rifampin, a semisynthetic rifamycin, is the cornerstone of current tuberculosis treatment. Among many semisynthetic rifamycins, benzoxazinorifamycins have great potential for TB treatment due to their superior affinity for wild-type and rifampin-resistant Mycobacterium tuberculosis RNA polymerases and their reduced hepatic Cyp450 induction activity. In this study, we have determined the crystal structures of the Escherichia coli RNA polymerase complexes with two benzoxazinorifamycins. The ansa-naphthalene moieties of the benzoxazinorifamycins bind in a deep pocket of the beta subunit, blocking the path of the RNA transcript. The C3'-tail of benzoxazinorifamycin fits a cavity between the beta subunit and sigma factor. We propose that in addition to blocking RNA exit, the benzoxazinorifamycin C3'-tail changes the sigma region 3.2 loop position, which influences the template DNA at the active site, thereby reducing the efficiency of transcription initiation. This study supports expansion of structure-activity relationships of benzoxazinorifamycins inhibition of RNA polymerase toward uncovering superior analogues with development potential.

X-ray Crystal Structures of the Escherichia coli RNA Polymerase in Complex with Benzoxazinorifamycins.,Molodtsov V, Nawarathne IN, Scharf NT, Kirchhoff PD, Showalter HD, Garcia GA, Murakami KS J Med Chem. 2013 Jun 13;56(11):4758-63. doi: 10.1021/jm4004889. Epub 2013 May 31. PMID:23679862^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Molodtsov V, Nawarathne IN, Scharf NT, Kirchhoff PD, Showalter HD, Garcia GA, Murakami KS. X-ray Crystal Structures of the Escherichia coli RNA Polymerase in Complex with Benzoxazinorifamycins. J Med Chem. 2013 Jun 13;56(11):4758-63. doi: 10.1021/jm4004889. Epub 2013 May 31. PMID:23679862 doi:10.1021/jm4004889

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4kmu"

@@ Line 9: / Line 9: @@
 <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4kmu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4kmu OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4kmu RCSB], [http://www.ebi.ac.uk/pdbsum/4kmu PDBsum]</span></td></tr>
 </table>
+== Function ==
+[[http://www.uniprot.org/uniprot/RPOZ_ECOLI RPOZ_ECOLI]] Promotes RNA polymerase assembly. Latches the N- and C-terminal regions of the beta' subunit thereby facilitating its interaction with the beta and alpha subunits.[HAMAP-Rule:MF_00366] [[http://www.uniprot.org/uniprot/RPOA_ECOLI RPOA_ECOLI]] DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. This subunit plays an important role in subunit assembly since its dimerization is the first step in the sequential assembly of subunits to form the holoenzyme.[HAMAP-Rule:MF_00059] [[http://www.uniprot.org/uniprot/RPOC_ECOLI RPOC_ECOLI]] DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates.[HAMAP-Rule:MF_01322] [[http://www.uniprot.org/uniprot/RPOB_ECOLI RPOB_ECOLI]] DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates.[HAMAP-Rule:MF_01321] [[http://www.uniprot.org/uniprot/RPOD_ECOLI RPOD_ECOLI]] Sigma factors are initiation factors that promote the attachment of RNA polymerase to specific initiation sites and are then released. This is the primary sigma factor of this bacterium.
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==

4kmu

From Proteopedia

Revision as of 22:23, 25 December 2014

X-ray crystal structure of the Escherichia coli RNA polymerase in complex with Rifampin

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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