4kn4

X-ray crystal structure of the Escherichia coli RNA polymerase in complex with Benzoxazinorifamycin-2b

spinqualitylabelsall models 4kn4, resolution 3.96Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4kn4 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. Method: X-ray diffraction, Resolution 3.965Å Ligands: 1RL, MG, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function 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] 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also N-acetylglucosamine-1-phosphate uridyltransferase RNA polymerase 3D structures Sigma factor 3D structures

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