Mycobacterium tuberculosis structure

Bamlcetin a pyrimidine antibiotic (see Nucleoside antibiotics) synthesized by Streptomyces plicatus. It is effective in low concentrations against Mycobacterium tuberculosis. Structurally, it is very similar to Amicetin (see), differing merely in the structure of the amosamine moiety which possesses a monome-thylamino group in place of the dimethylamino group. 

The thiophene analog of chloramphenicol (255) has been synthesized,as also have been similar structures. The antibacterial activity of all was much lower than that of the natural antibiotic. The thioamide of 2-thenoic acid has been prepared in a study of potential antitubercular compounds. It did not surpass thioisonico-tinamide in antitubercular activity. The thiosemicarbazones of thio-phenealdehydes and ketones (cf. Section VII,D) show high activity against Mycobacterium tuberculosis, but are very toxic. The thiosemi-carbazone of 4-(2-thienyl)-3-buten-2-one has been reported to be capable of completely inhibiting the in vitro growth of M. tuberculosis even in relatively low concentrations. ... 

Bertrand T, NAJ Eady, IN Jones, Jesmin, JM Nagy, B Jamart-Gregoire, EL Raven, KA Brown (2004) Crystal structure of Mycobacterium tuberculosis catalase-peroxidase. J Biol Chem 279 38991-38999. 

Since the causative organism of leprosy, one of the world s six major diseases, Mycobacterium leprae, is closely related to Mycobacterium tuberculosis, thio-semicarbazones have also been used as second-line drugs in the chemotherapy of leprosy [38]. The most widely used in leprosy treatment has been thiacetazone, and structure-activity relationships for it are similar to those observed for antitubercular thiosemicarbazones [39, 40]. 

In order to analyze the effect that conformational restriction has on the antibiotic enzymatic inactivation, three different enzymes were chosen as model systems Staphylococcus aureus ANT(4 ), Mycobacterium tuberculosis AAC(2 ) and Enterococcus faecalis APH(3 ). These proteins are representative of the three main families of enzymes that modify aminoglycosides adenyltrans-ferases, acyltransferases and phosphotransferases. In addition, there is high resolution X-ray structural information available for the three enzymes in complex with several antibiotics. 

Snow GA (1965) Isolation and Structure of Mycobactin T, a Growth Factor from Mycobacterium tuberculosis. Biochem J 97 166... 

X-ray crystal structures of glutamine synthetase from both Salmonella typhimuriuni and Mycobacterium tuberculosis are very similar. Structures of wild type enzymes and of active site mutants have been determined. All structures have been solved with Mn in the active site. There are twelve identical subunits arranged in two face-to-face symmetrical hexamers. The active sites are in funnel-shaped open-ended cavities located between adjacent subunits of the hexamer. These cavities are 45 A long, 30 A wide at the outer end, and 10 A wide at the inner end and the active site with the two Mn " ions is approximately halfway down the cavity. The metal-metal distance is 5.8 A. The more tightly bound Mn is coordinated to the side chains of Glu-131, Glu-212, Glu-220, and two water molecules, one of which is shared by both metal ions. Glu-129, Glu-357, His-269, and two additional water molecules are bound to the Mn + at the lower affinity site. A schematic view of the active site metal coordination is shown in Figure 36. 

In 1991, McChesney and El-Feraly described the isolation and structural elucidation of 3-formyl-6-methoxycarbazole (97) from the roots of C. lansium (23). The roots of this ornamental tree are used in traditional medicine in Taiwan to treat bronchitis and malaria (23). In 2005, Franzblau et al. isolated the same natural product from the stem bark of Micromelum hirsutum (103). They reported that 3-formyl-6-methoxycarbazole (97) shows in vitro anti-TB activity against the H37RV strain of Mycobacterium tuberculosis. 

Podust, L. M., Poulos, T. L., and Waterman, M. R. (2001) Crystal structure of cytochrome P450 14alpha-sterol demethylase (CYP51) from Mycobacterium tuberculosis in complex with azole inhibitors. Proc. Natl. Acad. Sci. USA 98, 3068-3073. 

Ansamycins, like the macrolides, are synthesized by condensation of a number of acetate and propionate units. These antibiotics, which are produced by several genera of the Actinomy-cetales, display a characteristic core aromatic ring structure. Amongst the best-known family members are the rifamycins, which are particularly active against Gram-positive bacteria and mycobacteria. They have been used, for example, in the treatment of Mycobacterium tuberculosis. 

Susceptible strains of Mycobacterium tuberculosis and other mycobacteria are inhibited in vitro by ethambutol, 1-5 mcg/mL. Ethambutol inhibits mycobacterial arabinosyl transferases, which are encoded by the embCAB operon. Arabinosyl transferases are involved in the polymerization reaction of arabinoglycan, an essential component of the mycobacterial cell wall. Resistance to ethambutol is due to mutations resulting in overexpression of emb gene products or within the embB structural gene. 

Fioravanti, E. Haouz, A. Ursby, T. Munier-Lehmann, H. Delarue, M. Bourgeois, D. Mycobacterium tuberculosis thymidylate kinase structural studies of intermediates along the reaction pathway. J. Mol. Biol., 327, 1077-1092 (2003)... 

The Mexican sponge Aplysina gerardogreeni contains calafianin (2106) (1880) (structure revised and confirmed by total synthesis, (1881-1883)), the known aerothionin, and the new phenylacetic acid 2107 (1880). These studies confirm that calafianin (2106) and aerothionin have the same absolute configuration (1883). Whereas aerothionin displays antibacterial activity against Mycobacterium tuberculosis, calafianin does not (1884). The Brazilian sponge Aplysina caissara contains the new caissarines A (2108) and B (2109) (1885). 

Raman K, Yeturu K, Chandra N (2008) TargetTB a target identification pipeline for Mycobacterium tuberculosis through an interac-tome, reactome and genome-scale structural analysis. BMC Syst Biol 2 109... 

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