3DXJ

Crystal structure of thermus thermophilus rna polymerase holoenzyme in complex with the antibiotic myxopyronin

Summary for 3DXJ

• Entry DOI: 10.2210/pdb3dxj/pdb
• Related: 1IW7 1ZYR
• Descriptor: DNA-directed RNA polymerase subunit alpha; CHAIN A, B, K, L, methyl [(1E,5R)-5-{(3S)-3-[(2E,4E)-2,5-dimethylocta-2,4-dienoyl]-2,4-dioxo-3,4-dihydro-2H-pyran-6-yl}hexylidene]carbamate, BACTERIAL RNA POLYMERASE BETA SUBUNIT; CHAIN C, M, ... (11 entities in total)
• Functional Keywords: rna polymerase; rnap; drug complex; inhibitor; corallopyronin; ripostatin; transcription; holoenzyme; crystallography; twinning; hemihedral, dna-directed rna polymerase, nucleotidyltransferase, transcription, transferase, dna-binding, sigma factor, transcription regulation
• Biological source: Thermus thermophilus HB8; More
• Total number of polymer chains: 12
• Total formula weight: 855045.03

Authors

Das, K.,Arnold, E. (deposition date: 2008-07-24, release date: 2008-10-14, Last modification date: 2023-08-30)

Primary citation

Mukhopadhyay, J.,Das, K.,Ismail, S.,Koppstein, D.,Jang, M.,Hudson, B.,Sarafianos, S.,Tuske, S.,Patel, J.,Jansen, R.,Irschik, H.,Arnold, E.,Ebright, R.H.
The RNA polymerase "switch region" is a target for inhibitors.
Cell(Cambridge,Mass.), 135:295-307, 2008

PubMed Abstract: The alpha-pyrone antibiotic myxopyronin (Myx) inhibits bacterial RNA polymerase (RNAP). Here, through a combination of genetic, biochemical, and structural approaches, we show that Myx interacts with the RNAP "switch region"--the hinge that mediates opening and closing of the RNAP active center cleft--to prevent interaction of RNAP with promoter DNA. We define the contacts between Myx and RNAP and the effects of Myx on RNAP conformation and propose that Myx functions by interfering with opening of the RNAP active-center cleft during transcription initiation. We further show that the structurally related alpha-pyrone antibiotic corallopyronin (Cor) and the structurally unrelated macrocyclic-lactone antibiotic ripostatin (Rip) function analogously to Myx. The RNAP switch region is distant from targets of previously characterized RNAP inhibitors, and, correspondingly, Myx, Cor, and Rip do not exhibit crossresistance with previously characterized RNAP inhibitors. The RNAP switch region is an attractive target for identification of new broad-spectrum antibacterial therapeutic agents.

PubMed: 18957204
DOI: 10.1016/j.cell.2008.09.033

Experimental method

X-RAY DIFFRACTION (3 Å)