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Expression And Identification Of M.tuberculosis RmlC Enzyme

Posted on:2007-04-03Degree:MasterType:Thesis
Country:ChinaCandidate:L ShiFull Text:PDF
GTID:2120360185470525Subject:Biochemistry and Molecular Biology
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Tuberculosis (TB) is a kind of ancient disease, endangering the human being's health seriously, is also the public hygiene problem and social problems of the global concern. Major problem is the impressive emergence and wide distribution of multidrug-resistant strains of Mycobacterium tuberculosis. The mortality resulting from infection of M. tuberculosis has been increasing globally, but no tuberculosis-specific drugs have been discovered in 40 years. Therefore, there is a desperate need for new effective anti-TB drugs to prevent and treat TB.The targets of new drugs need to be validated during drug discovery. The mycobacterial cell wall is required for the survival and growth of mycobacteria in the host, and has the unique components and structures. So, mycobacterial cell wall is a target to develop new anti-TB drugs. The disaccharidelinker (L-rhamnosyl-N-acetyl-glucosaminyl-phosphate) is fundamental to the structural integrity of the mycobacterial cell wall. The L-rhamnosyl residue in the disaccharide linker is provided with a sugar donor, dTDP-rhamnose (dTDP-Rha), and L-Rha is not found in humans. Therefore, the enzymes (RmlA, RmlB, RmlC and RmlD) involved in the formation of dTDP-Rha are important drug targets to develop new effective anti-TB drugs. The inhibitors that inhibit RmlA,RmlB,RmlC or RmlD could be new anti-TB drugs.dTDP-4-keto-6-deoxy-D-glucose 3, 5 epimerase (RmlC) is encoded by rmlC gene. Recent research showed that rmlC is an essential gene for the survival and growth of mycobacteria.In order to establish a molecular model based on RmlC enzyme assay to screen inhibitors of RmlC, a large amount of RmlC protein must be acquired. Soluble RmlC protein will be utilized for further development of a quick and accurate enzyme assay and study of...
Keywords/Search Tags:M.tuberculosis, dTDP-4-keto-6-deoxy-D-glucose3,5 epimerase, rmlC gene, Molecular chaperone, M.Smegmais
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