PDBsum entry 4oin

Transcription, transferase/antibiotic

PDB id: 4oin

Contents

Protein chains

231 a.a.

1112 a.a.

1485 a.a.

94 a.a.

346 a.a.

DNA/RNA

Ligands

2RA-DSN-DVA-R2T-2TL-0QZ-FGL

MB8

Metals

_MG ×5

_ZN ×2

Waters ×622

PDB id:

4oin

Name:

Transcription, transferase/antibiotic

Title:

Crystal structure of thermus thermophilus transcription initiation complex soaked with ge23077

Structure:

DNA-directed RNA polymerase subunit alpha. Chain: a, b. Synonym: rnap subunit alpha, RNA polymerase subunit alpha, transcriptase subunit alpha. DNA-directed RNA polymerase subunit beta. Chain: c. Synonym: rnap subunit beta, RNA polymerase subunit beta, transcriptase subunit beta. DNA-directed RNA polymerase subunit beta'.

Source:

Thermus thermophilus. Organism_taxid: 300852. Strain: hb8 / atcc 27634 / dsm 579. Gene: rpod, ttha0532. Expressed in: escherichia coli. Expression_system_taxid: 469008. Synthetic: yes. Actinomadura sp.. Organism_taxid: 1989

Resolution:

2.80Å R-factor: 0.208 R-free: 0.252

Authors:

Y.Zhang,R.H.Ebright,E.Arnold

Key ref:

Y.Zhang et al. (2014). GE23077 binds to the RNA polymerase 'i' and 'i+1' sites and prevents the binding of initiating nucleotides. Elife, 3, e02450. PubMed id: 24755292 DOI: 10.7554/eLife.02450

Date:

20-Jan-14 Release date: 07-May-14

Protein chains

Q5SHR6  (RPOA_THET8) -  DNA-directed RNA polymerase subunit alpha from Thermus thermophilus (strain ATCC 27634 / DSM 579 / HB8)

Seq: 315 a.a.

Struc: 231 a.a.

Protein chain

Q8RQE9  (RPOB_THET8) -  DNA-directed RNA polymerase subunit beta from Thermus thermophilus (strain ATCC 27634 / DSM 579 / HB8)

Seq: 1119 a.a.

Struc: 1112 a.a.

Protein chain

Q8RQE8  (RPOC_THET8) -  DNA-directed RNA polymerase subunit beta' from Thermus thermophilus (strain ATCC 27634 / DSM 579 / HB8)

Seq: 1524 a.a.

Struc: 1485 a.a.

Protein chain

Q8RQE7  (RPOZ_THET8) -  DNA-directed RNA polymerase subunit omega from Thermus thermophilus (strain ATCC 27634 / DSM 579 / HB8)

Seq: 99 a.a.

Struc: 94 a.a.

Protein chain

Q5SKW1  (Q5SKW1_THET8) -  RNA polymerase sigma factor SigA from Thermus thermophilus (strain ATCC 27634 / DSM 579 / HB8)

Seq: 423 a.a.

Struc: 346 a.a.

DNA/RNA chains

G-C-A-T-C-C-G-T-G-A-G-T-C-G-A-G 16 bases

T-A-T-A-A-T-G-G-G-A-G-C-T-G-T-C-A-C-G-G-A-T-G-C 24 bases

Enzyme reactions

• Enzyme class: Chains A, B, C, D, E: E.C.2.7.7.6 - DNA-directed Rna polymerase.
• Reaction: RNA(n) + a ribonucleoside 5'-triphosphate = RNA(n+1) + diphosphate

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

Added reference

DOI no: 10.7554/eLife.02450

Elife 3:e02450 (2014)

PubMed id: 24755292

GE23077 binds to the RNA polymerase 'i' and 'i+1' sites and prevents the binding of initiating nucleotides.

Y.Zhang, D.Degen, M.X.Ho, E.Sineva, K.Y.Ebright, Y.W.Ebright, V.Mekler, H.Vahedian-Movahed, Y.Feng, R.Yin, S.Tuske, H.Irschik, R.Jansen, S.Maffioli, S.Donadio, E.Arnold, R.H.Ebright.

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.