3dxj

From Proteopedia

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

PDB ID 3dxj

Drag the structure with the mouse to rotate

Structural highlights

3dxj is a 12 chain structure with sequence from Thermus thermophilus HB8. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 3Å
Ligands:	, , , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

RPOA_THET8 DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates.

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

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.

The RNA polymerase "switch region" is a target for inhibitors.,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 RH Cell. 2008 Oct 17;135(2):295-307. PMID:18957204^[1]

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

References

↑ 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 RH. The RNA polymerase "switch region" is a target for inhibitors. Cell. 2008 Oct 17;135(2):295-307. PMID:18957204 doi:10.1016/j.cell.2008.09.033