T7 RNA Polymerase is an RNA polymerase from the T7 bacteriophage that catalyzes the formation of RNA from DNA in the 5'→ 3' direction.
44-496: (Redirected from SP-6 ) SP6 may refer to : SP6 RNA polymerase , a RNA polymerase related to the T7 RNA polymerase one of the three versions of the 9x39 mm rifle cartridge a model of steam toy made by British manufacturer Mamod Service pack 6 in computing 4685 Karetnikov (1978 SP6), a Main-belt Asteroid discovered on September 27, 1978 9154 Kolʹtsovo (1982 SP6),
88-495: A DNA-RNA hybrid of 8bp. A beta-hairpin specificity loop (residues 739-770 in T7) recognizes the promoter; swapping it out for one found in T3 RNAP makes the polymerase recognize T3 promoters instead. Similar to other viral nucleic acid polymerases , including T7 DNA polymerase from the same phage, the conserved C-terminal of T7 ssRNAP employs a fold whose organization has been likened to
132-464: A Main-belt Asteroid discovered on September 16, 1982 Spleen 6, an acupuncture point above the ankle on the inside of the leg. Specialist 6, an obsolete enlisted rank in the United States Army . See Specialist (rank) . Surface Pro 6 , a 2-in-1 detachable tablet computer developed by Microsoft Socket SP6 , a CPU socket for AMD server CPUs [REDACTED] Topics referred to by
176-525: A benign side effect that nonetheless can be frightening if it is not expected. This may also be used to monitor effective absorption of the drug (if drug color is not seen in the urine, the patient may wish to move the drug dose farther in time from food or milk intake). The discolorization of sweat and tears is not directly noticeable, but sweat may stain light clothing orange, and tears may permanently stain soft contact lenses. Since rifampicin may be excreted in breast milk, breastfeeding should be avoided while it
220-414: A consequence, can make them less effective, or even ineffective, by decreasing their levels. For instance, patients undergoing long-term anticoagulation therapy with warfarin have to increase their dosage of warfarin and have their clotting time checked frequently because failure to do so could lead to inadequate anticoagulation, resulting in serious consequences of thromboembolism. Rifampicin can reduce
264-581: A few days as prophylaxis against meningitis, but resistance develops quickly during long-term treatment of active infections, so the drug is always used against active infections in combination with other antibiotics. Rifampicin is relatively ineffective against spirochetes , which has led to its use as a selective agent capable of isolating them in materials being cultured in laboratories. Rifampicin has some effectiveness against vaccinia virus. The minimum inhibitory concentrations of rifampicin for several medically significant pathogens are: Rifampicin
308-483: A new class of molecules with antibiotic activity. Because Sensi, Timbal and the researchers were particularly fond of the French crime story Rififi (about a jewel heist and rival gangs), they decided to call these compounds rifamycins . After two years of attempts to obtain more stable semisynthetic products, a new molecule with high efficacy and good tolerability was produced in 1965 and was named rifampicin. Rifampicin
352-534: A red or orange color. Liver problems or allergic reactions may occur. It is part of the recommended treatment of active tuberculosis during pregnancy, though its safety in pregnancy is not known. Rifampicin is of the rifamycin group of antibiotics. It works by decreasing the production of RNA by bacteria. Rifampicin was discovered in 1965, marketed in Italy in 1968, and approved in the United States in 1971. It
396-925: Is also recommended as an alternative treatment for infections by the tick-borne pathogens Borrelia burgdorferi and Anaplasma phagocytophilum when treatment with doxycycline is contraindicated, such as in pregnant women or in patients with a history of allergy to tetracycline antibiotics. It is also sometimes used to treat infections by Listeria species, Neisseria gonorrhoeae , Haemophilus influenzae , and Legionella pneumophila . For these nonstandard indications, antimicrobial susceptibility testing should be done (if possible) before starting rifampicin therapy. The Enterobacteriaceae , Acinetobacter species, and Pseudomonas species are intrinsically resistant to rifampicin. It has been used with amphotericin B in largely unsuccessful attempts to treat primary amoebic meningoencephalitis caused by Naegleria fowleri . Rifampicin can be used as monotherapy for
440-502: Is antagonistic to the microbiologic effects of the antibiotics gentamicin and amikacin. The activity of rifampicin against some species of mycobacteria can be potentiated by isoniazid (through inhibiting mycolate synthesis) and ambroxol (through host directed effects in autophagy and pharmacokinetics). Rifampicin inhibits bacterial DNA-dependent RNA synthesis by inhibiting bacterial DNA-dependent RNA polymerase . Crystal structure data and biochemical data suggest that rifampicin binds to
484-472: Is being taken. Other adverse effects include: Rifampicin is a polyketide belonging to the chemical class of compounds termed ansamycins , so named because of their heterocyclic structure containing a naphthoquinone core spanned by an aliphatic ansa chain. The naphthoquinonic chromophore gives rifampicin its characteristic red-orange crystalline color. The critical functional groups of rifampicin in its inhibitory binding of bacterial RNA polymerase are
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#1732881140884528-611: Is commonly used to transcribe DNA that has been cloned into vectors that have two (different) phage promoters (e.g., T7 and T3, or T7 and SP6) in opposite orientation. RNA can be selectively synthesized from either strand of the insert DNA with the different polymerases. The enzyme is stimulated by spermidine and in vitro activity is increased by the presence of carrier proteins (such as BSA ). Homogeneously labeled single-stranded RNA can be generated with this system. Transcripts can be non-radioactively labeled to high specific activity with certain labeled nucleotides. T7 RNA polymerase
572-519: Is critical in improving patient outcomes by instituting appropriate second-line treatments, and in decreasing transmission of drug-resistant TB. Traditional methods of detecting resistance involve mycobacterial culture and drug susceptibility testing, results of which could take up to 6 weeks. Xpert MTB/RIF assay is an automated test that can detect rifampicin resistance, and also diagnose tuberculosis. A Cochrane review updated in 2014 and 2021 concluded that for rifampicin resistance detection, Xpert MTB/RIF
616-436: Is different from Wikidata All article disambiguation pages All disambiguation pages T7 RNA polymerase T7 polymerase is extremely promoter -specific and transcribes only DNA downstream of a T7 promoter. The T7 polymerase also requires a double stranded DNA template and Mg ion as cofactor for the synthesis of RNA. It has a very low error rate. T7 polymerase has a molecular weight of 99 kDa. The promoter
660-406: Is easily absorbed from the gastrointestinal (GI) tract; its ester functional group is quickly hydrolyzed in bile , and it is catalyzed by a high pH and substrate-specific esterases . After about 6 hours, almost all of the drug is deacetylated. Even in this deacetylated form, rifampicin is still a potent antibiotic; however, it can no longer be reabsorbed by the intestines and is eliminated from
704-507: Is on the World Health Organization's List of Essential Medicines . The World Health Organization classifies rifampicin as critically important for human medicine. It is available as a generic medication . Rifampicin is made by the soil bacterium Amycolatopsis rifamycinica . Rifampicin is used for the treatment of tuberculosis in combination with other antibiotics, such as pyrazinamide , isoniazid , and ethambutol . For
748-497: Is recognized for binding and initiation of the transcription. The consensus in T7 and related phages is: Transcription begins at the asterisk-marked guanine. T7 polymerase has been crystallised in several forms and the structures placed in the PDB . These explain how T7 polymerase binds to DNA and transcribes it. The N-terminal domain moves around as the elongation complex forms. The ssRNAP holds
792-516: Is strongly recommended" for latent TB infection; and when used as post-exposure prophylaxis to prevent Haemophilus influenzae type b and meningococcal disease in people who have been exposed to those bacteria. Before treating a person for a long period of time, measurements of liver enzymes and blood counts are recommended. Rifampicin may be given either by mouth or intravenously. Common side effects include nausea, vomiting, diarrhea, and loss of appetite. It often turns urine, sweat, and tears
836-441: Is taken with a meal, its peak blood concentration falls by 36%. Antacids do not affect its absorption. The decrease in rifampicin absorption with food is sometimes enough to noticeably affect urine color, which can be used as a marker for whether or not a dose of the drug has been effectively absorbed. Distribution of the drug is high throughout the body, and reaches effective concentrations in many organs and body fluids, including
880-463: Is through Arr-catalyzed ADP-ribosylation of rifampicin. With the assistance of the enzyme Arr produced by the pathogen Mycobacterium smegmatis , ADP-ribose is added to rifampicin at one of its ansa chain hydroxy groups, thereby inactivating the drug. Mycobacterial resistance to rifampicin may occur alone or along with resistance to other first-line antitubercular drugs. Early detection of such multidrug or extensively drug-resistant tuberculosis
924-475: Is used in the synthesis of mRNA and sgRNA. Rifampicin Rifampicin , also known as rifampin , is an ansamycin antibiotic used to treat several types of bacterial infections , including tuberculosis (TB), Mycobacterium avium complex , leprosy , and Legionnaires' disease . It is almost always used together with other antibiotics with two notable exceptions: when given as a "preferred treatment that
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#1732881140884968-461: Is used to treat itchiness caused by primary biliary cholangitis . The treatment-related adverse effects include hepatotoxicity , nephrotoxicity , hemolysis , and interactions with other drugs. For those reasons as well as some ethical concerns regarding off-label use of antibiotics, rifampin as a very effective preventive antibiotic for meningitis, is not considered appropriate for itchiness. Rifampicin with clindamycin has been used to treat
1012-411: The rpoB gene, encoding the beta subunit of RNA polymerase. The majority of resistance mutations in E. coli are in 3 clusters on rpoB . Cluster I is amino acids 509 to 533, cluster II is amino acids 563 to 572, and cluster III is amino acid 687. When describing mutations in rpoB in other species, the corresponding amino acid number in E. coli is usually used. In Mycobacterium tuberculosis ,
1056-418: The cerebrospinal fluid . Since the substance itself is red, this high distribution is the reason for the orange-red color of the saliva, tears, sweat, urine, and feces. About 60% to 90% of the drug is bound to plasma proteins. Rifampicin inhibits bacterial RNA polymerase, and is commonly used to inhibit the synthesis of host bacterial proteins during recombinant protein expression in bacteria. RNA encoding for
1100-508: The 5' end of the RNA transcript past more than two or three nucleotides. In a recent study rifampicin was shown to bind to cytochrome P450 reductase and alter its conformation as well as activity towards supporting metabolism of progesterone via CYP21A2 . Resistance to rifampicin arises from mutations that alter residues of the rifampicin binding site on RNA polymerase, resulting in decreased affinity for rifampicin. Resistance mutations map to
1144-669: The FDA continues to investigate the presence of 1-methyl-4-nitrosopiperazine (MNP) in rifampin or 1-cyclopentyl-4-nitrosopiperazine (CPNP) in rifapentine approved for sale in the US. Rifampicin is the INN and BAN , while rifampin is the USAN . Rifampicin may be abbreviated R, RMP, RA, RF, or RIF (US). Rifampicin is also known as rifaldazine, rofact, and rifampin in the United States, also as rifamycin SV. Its chemical name
1188-481: The body. Only about 7% of the administered drug is excreted unchanged in urine, though urinary elimination accounts for only about 30% of the drug excretion. About 60% to 65% is excreted through feces. The half-life of rifampicin ranges from 1.5 to 5.0 hours, though hepatic impairment significantly increases it. Food consumption inhibits its absorption from the GI tract, and the drug is more quickly eliminated. When rifampicin
1232-401: The development of active disease because only small numbers of bacteria are present. A Cochrane review found no difference in efficacy between a 3- to 4-month regimen of rifampicin and a 6-month regimen of isoniazid for preventing active tuberculosis in patients not infected with HIV, and patients who received rifampicin had a lower rate of hepatotoxicity . However, the quality of the evidence
1276-588: The efficacy of birth control pills or other hormonal contraception by its induction of the cytochrome P450 system, to the extent that unintended pregnancies have occurred in women who use oral contraceptives and took rifampicin even for very short courses (for example, as prophylaxis against exposure to bacterial meningitis). Other interactions include decreased levels and less effectiveness of antiretroviral agents , everolimus , atorvastatin , rosiglitazone , pioglitazone , celecoxib , clarithromycin , caspofungin , voriconazole , and lorazepam . Rifampicin
1320-480: The four critical hydroxyl groups of the ansa bridge and the naphthol ring, which form hydrogen bonds with amino acid residues on the protein. Rifampicin is the 3-(4-methyl-1-piperazinyl)-iminomethyl derivative of rifamycin SV . Rifampicin is the most powerful known inducer of the hepatic cytochrome P450 enzyme system, including isoenzymes CYP2B6 , CYP2C8 , CYP2C9 , CYP2C19 , CYP3A4 , CYP3A5 , and CYP3A7 . It increases metabolism of many drugs and as
1364-559: The majority of mutations leading to rifampicin resistance are in cluster I, in a 81bp hotspot core region called RRDR for "rifampcin resistance determining region". A change in amino acid 531 from serine to leucine arising from a change in the DNA sequence of TCG to TTG is the most common mutation. Tuberculosis resistance has also occurred due to mutations in the N-terminal region of rpoB and cluster III. An alternative mechanism of resistance
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1408-482: The mitochondrial RNA polymerase ( POLRMT ), and the chloroplastic ssRNAP. The ssRNAP family is structurally and evolutionarily distinct from the multi-subunit family of RNA polymerases (including bacterial and eukaryotic sub-families). In contrast to bacterial RNA polymerases, T7 polymerase is not inhibited by the antibiotic rifampicin . This family is related to single-subunit reverse transcriptase and DNA polymerase . In biotechnology applications, T7 RNA polymerase
1452-446: The nitrosamine class of compounds, some of which are classified as probable or possible human carcinogens (substances that could cause cancer), based on laboratory tests such as rodent carcinogenicity studies. Although there are no data available to directly evaluate the carcinogenic potential of MNP, information available on closely related nitrosamine compounds was used to calculate lifetime exposure limits for MNP. As of January 2021,
1496-463: The pocket of the RNA polymerase β subunit within the DNA/RNA channel, but away from the active site. 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
1540-571: The recombinant gene is usually transcribed from DNA by a viral T7 RNA polymerase , which is not affected by rifampicin. In 1957, a soil sample from a pine forest on the French Riviera was brought for analysis to the Lepetit Pharmaceuticals research lab in Milan , Italy. There, a research group headed by Piero Sensi and Maria Teresa Timbal discovered a new bacterium. This new species produced
1584-448: The same term This disambiguation page lists articles associated with the same title formed as a letter–number combination. If an internal link led you here, you may wish to change the link to point directly to the intended article. Retrieved from " https://en.wikipedia.org/w/index.php?title=SP6&oldid=1220964505 " Category : Letter–number combination disambiguation pages Hidden categories: Short description
1628-400: The shape of a right hand with three subdomains termed fingers, palm, and thumb. The N-terminal is less conserved. It forms a promoter-binding domain (PBD) with helix bundles in phage ssRNAPs, a feature not found in mitochondrial ssRNAPs. T7 polymerase is a representative member of the single-subunit DNA-dependent RNAP (ssRNAP) family. Other members include phage T3 and SP6 RNA polymerases,
1672-448: The skin disease hidradenitis suppurativa . The most serious adverse effect is hepatotoxicity, and people receiving it often undergo baseline and frequent liver function tests to detect early liver damage. The more common side effects include fever, gastrointestinal disturbances, rashes, and immunological reactions. Taking rifampicin usually causes certain bodily fluids, such as urine, sweat, and tears, to become orange-red in color,
1716-653: The standard treatment of Hansen's disease, rifampicin is always used in combination with dapsone and clofazimine to avoid causing drug resistance. It is also used in the treatment of Mycobacterium ulcerans infections as associated with Buruli ulcer , usually in combination with clarithromycin or other antibiotics. In 2008, tentative evidence showed rifampicin may be useful in the treatment of methicillin-resistant Staphylococcus aureus ( MRSA ) in combination with other antibiotics, including in difficult-to-treat infections such as osteomyelitis and prosthetic joint infections. As of 2012, if rifampicin combination therapy
1760-521: The treatment of tuberculosis, it is administered daily for at least six months. Combination therapy is used to prevent the development of resistance and to shorten the length of treatment. Resistance of Mycobacterium tuberculosis to rifampicin develops quickly when it is used without another antibiotic, with laboratory estimates of resistance rates from 10 to 10 per tuberculosis bacterium per generation. Rifampicin can be used alone in patients with latent tuberculosis infections to prevent or delay
1804-442: Was accurate, that is (95%) sensitive and (98%) specific. Orally administered rifampicin results in peak plasma concentrations in about 2–4 hours. 4-Aminosalicylic acid (another antituberculosis drug) significantly reduces absorption of rifampicin, and peak concentrations may be lower. If these two drugs must be used concurrently, they must be given separately, with an interval of 8 to 12 hours between administrations. Rifampicin
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1848-435: Was first sold in Italy in 1968 and was approved by the FDA in 1971. In August 2020, the U.S. Food and Drug Administration (FDA) became aware of nitrosamine impurities in certain samples of rifampin. The FDA and manufacturers are investigating the origin of these impurities in rifampin, and the agency is developing testing methods for regulators and industry to detect the 1-methyl-4-nitrosopiperazine (MNP). MNP belongs to
1892-518: Was judged to be low. A shorter 2-month course of rifampicin and pyrazinamide had previously been recommended but is no longer recommended due to high rates of hepatotoxicity. Rifampicin should be taken on an empty stomach with a glass of water. It is generally taken either at least one hour before meals or two hours after meals. Rifampicin is also used to treat nontuberculous mycobacterial infections including leprosy (Hansen's disease) and Mycobacterium kansasii . With multidrug therapy used as
1936-399: Was useful for pyogenic vertebral osteomyelitis was unclear. A meta-analysis concluded that adding adjunctive rifampicin to a β-lactam or vancomycin may improve outcomes in staphylococcus aureus bacteremia. However, a more recent trial found no benefit from adjunctive rifampicin. It is also used as preventive treatment against Neisseria meningitidis ( meningococcal ) infections. Rifampicin
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