Rifampicin
From Proteopedia
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Crystal structure data and biochemical data suggest that <scene name='10/1022377/Cv/4'>rifampicin binds to the pocket of the RNA polymerase β subunit</scene> within the DNA/RNA channel, but away from the active site.<ref name="a39">PMID:11290327</ref> The inhibitor prevents RNA synthesis by physically blocking elongation, and thus preventing synthesis of host bacterial proteins. By this "steric-occlusion" mechanism, rifampicin blocks synthesis of the second or third phosphodiester bond between the nucleotides in the RNA backbone, preventing elongation of the 5' end of the RNA transcript past more than 2 or 3 nucleotides.<ref name="a39">PMID:11290327</ref><ref name="a49">PMID:18787125</ref> | Crystal structure data and biochemical data suggest that <scene name='10/1022377/Cv/4'>rifampicin binds to the pocket of the RNA polymerase β subunit</scene> within the DNA/RNA channel, but away from the active site.<ref name="a39">PMID:11290327</ref> The inhibitor prevents RNA synthesis by physically blocking elongation, and thus preventing synthesis of host bacterial proteins. By this "steric-occlusion" mechanism, rifampicin blocks synthesis of the second or third phosphodiester bond between the nucleotides in the RNA backbone, preventing elongation of the 5' end of the RNA transcript past more than 2 or 3 nucleotides.<ref name="a39">PMID:11290327</ref><ref name="a49">PMID:18787125</ref> | ||
| - | In a recent study Rifampicin was shown to bind to [[NADPH-Cytochrome P450 Reductase|cytochrome P450 reductase]] and alter its conformation as well as activity towards supporting metabolism of progesterone via CYP21A2.<ref name="a50">PMID:33859207</ref> | + | In a recent study Rifampicin was shown to bind to [[NADPH-Cytochrome P450 Reductase|cytochrome P450 reductase]] and alter its conformation as well as activity towards supporting metabolism of [[progesterone]] via CYP21A2.<ref name="a50">PMID:33859207</ref> |
</StructureSection> | </StructureSection> | ||
== References == | == References == | ||
<references/> | <references/> | ||
Current revision
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References
- ↑ 1.0 1.1 "Rifampin". The American Society of Health-System Pharmacists. Archived from the original on 2015-09-07. Retrieved Aug 1, 2015.
- ↑ Sterling TR, Njie G, Zenner D, Cohn DL, Reves R, Ahmed A, Menzies D, Horsburgh CR Jr, Crane CM, Burgos M, LoBue P, Winston CA, Belknap R. Guidelines for the Treatment of Latent Tuberculosis Infection: Recommendations from the National Tuberculosis Controllers Association and CDC, 2020. MMWR Recomm Rep. 2020 Feb 14;69(1):1-11. PMID:32053584 doi:10.15585/mmwr.rr6901a1
- ↑ Calvori C, Frontali L, Leoni L, Tecce G. Effect of rifamycin on protein synthesis. Nature. 1965 Jul 24;207(995):417-8. PMID:4957347 doi:10.1038/207417a0
- ↑ 4.0 4.1 Campbell EA, Korzheva N, Mustaev A, Murakami K, Nair S, Goldfarb A, Darst SA. Structural mechanism for rifampicin inhibition of bacterial rna polymerase. Cell. 2001 Mar 23;104(6):901-12. PMID:11290327
- ↑ Feklistov A, Mekler V, Jiang Q, Westblade LF, Irschik H, Jansen R, Mustaev A, Darst SA, Ebright RH. Rifamycins do not function by allosteric modulation of binding of Mg2+ to the RNA polymerase active center. Proc Natl Acad Sci U S A. 2008 Sep 30;105(39):14820-5. PMID:18787125 doi:10.1073/pnas.0802822105
- ↑ Jensen SB, Thodberg S, Parween S, Moses ME, Hansen CC, Thomsen J, Sletfjerding MB, Knudsen C, Del Giudice R, Lund PM, Castaño PR, Bustamante YG, Velazquez MNR, Jørgensen FS, Pandey AV, Laursen T, Møller BL, Hatzakis NS. Biased cytochrome P450-mediated metabolism via small-molecule ligands binding P450 oxidoreductase. Nat Commun. 2021 Apr 15;12(1):2260. PMID:33859207 doi:10.1038/s41467-021-22562-w
