4OIQ: Crystal Structure Of Thermus Thermophilus Transcription Initiation Complex Soaked With Ge23077 And Rifampicin

Citation:
Abstract
Using a combination of genetic, biochemical, and structural approaches, we show that the cyclic-peptide antibiotic GE23077 (GE) binds directly to the bacterial RNA polymerase (RNAP) active-center 'i' and 'i+1' nucleotide binding sites, preventing the binding of initiating nucleotides, and thereby preventing transcription initiation. The target-based resistance spectrum for GE is unusually small, reflecting the fact that the GE binding site on RNAP includes residues of the RNAP active center that cannot be substituted without loss of RNAP activity. The GE binding site on RNAP is different from the rifamycin binding site. Accordingly, GE and rifamycins do not exhibit cross-resistance, and GE and a rifamycin can bind simultaneously to RNAP. The GE binding site on RNAP is immediately adjacent to the rifamycin binding site. Accordingly, covalent linkage of GE to a rifamycin provides a bipartite inhibitor having very high potency and very low susceptibility to target-based resistance. DOI: http://dx.doi.org/10.7554/eLife.02450.001.
PDB ID: 4OIQDownload
MMDB ID: 119603
PDB Deposition Date: 2014/1/20
Updated in MMDB: 2014/05
Experimental Method:
x-ray diffraction
Resolution: 3.62  Å
Source Organism:
Thermus thermophilus HB8
Similar Structures:
Biological Unit for 4OIQ: nonameric; determined by author
Molecular Components in 4OIQ
Label Count Molecule
Proteins (7 molecules)
2
DNA-directed RNA Polymerase Subunit Alpha(Gene symbol: TTHA1664)
Molecule annotation
1
DNA-directed RNA Polymerase Subunit Beta(Gene symbol: rpoB)
Molecule annotation
1
DNA-directed RNA Polymerase Subunit Beta'(Gene symbol: TTHA1812)
Molecule annotation
1
DNA-directed RNA Polymerase Subunit Omega(Gene symbol: rpoZ)
Molecule annotation
1
DNA Directed RNA Polymerase Sigma Factor a
Molecule annotation
1
Ge23077
Molecule annotation
Nucleotides(2 molecules)
1
5'-d(*cp*cp*t*gp*cp*ap*tp*cp*cp*gp*tp*gp*ap*gp*tp*cp*gp*ap* Gp*gp*g)-3'
Molecule annotation
1
5'-d(*tp*ap*tp*ap*ap*tp*gp*gp*gp*ap*gp*cp*tp*gp*tp*cp*ap*cp *gp*gp*ap*tp*gp*cp*ap*gp*g)-3'
Molecule annotation
Chemicals (7 molecules)
1
1
2
2
3
4
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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