6ccv

Crystal structure of a Mycobacterium smegmatis RNA polymerase transcription initiation complex with inhibitor Rifampicin

spinqualitylabelsall models 6ccv, resolution 3.05Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6ccv is a 11 chain structure with sequence from Mycolicibacterium smegmatis MC2 155 and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 3.05Å Ligands: EDO, GLU, RFP, SO4, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function RPOA_MYCS2 DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates.[HAMAP-Rule:MF_00059] Publication Abstract from PubMed Rifamycin antibiotics (Rifs) target bacterial RNA polymerases (RNAPs) and are widely used to treat infections including tuberculosis. The utility of these compounds is threatened by the increasing incidence of resistance (Rif(R)). As resistance mechanisms found in clinical settings may also occur in natural environments, here we postulated that bacteria could have evolved to produce rifamycin congeners active against clinically relevant resistance phenotypes. We survey soil metagenomes and identify a tailoring enzyme-rich family of gene clusters encoding biosynthesis of rifamycin congeners (kanglemycins, Kangs) with potent in vivo and in vitro activity against the most common clinically relevant Rif(R) mutations. Our structural and mechanistic analyses reveal the basis for Kang inhibition of Rif(R) RNAP. Unlike Rifs, Kangs function through a mechanism that includes interfering with 5'-initiating substrate binding. Our results suggest that examining soil microbiomes for new analogues of clinically used antibiotics may uncover metabolites capable of circumventing clinically important resistance mechanisms. Rifamycin congeners kanglemycins are active against rifampicin-resistant bacteria via a distinct mechanism.,Peek J, Lilic M, Montiel D, Milshteyn A, Woodworth I, Biggins JB, Ternei MA, Calle PY, Danziger M, Warrier T, Saito K, Braffman N, Fay A, Glickman MS, Darst SA, Campbell EA, Brady SF Nat Commun. 2018 Oct 8;9(1):4147. doi: 10.1038/s41467-018-06587-2. PMID:30297823 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Sigma factor 3D structures

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