From DrugPedia: A Wikipedia for Drug discovery

Revision as of 07:24, 31 January 2010

General

The gene iniA is primarily involved in mounting the drug tolerance in M.tuberculosis to drugs such as Isoniazid(INH) and Ethambutol(EMB).Little is known about the intracellular events that occur following the initial inhibition of Mycobacterium tuberculosis by the first-line antituberculosis drugs isoniazid (INH) and ethambutol (EMB). Understanding these pathways should provide significant insights into the adaptive strategies M. tuberculosis undertakes to survive antibiotics. This gene is strongly induced along with iniB and iniC (Rv 0341 and Rv 0343) by treatment of Mycobacterium bovis BCG or M. tuberculosis with INH or EMB. BCG strains overexpressing M. tuberculosis iniA grew and survived longer than control strains upon exposure to inhibitory concentrations of either INH or EMB. A M. tuberculosis strain containing an iniA deletion showed increased susceptibility to INH. Additional studies showed that overexpression of M. tuberculosis iniA in BCG conferred resistance to ethidium bromide, and the deletion of iniA in M. tuberculosis resulted in increased accumulation of intracellular ethidium bromide. The pump inhibitor reserpine reversed both tolerance to INH and resistance to ethidium bromide in BCG. These results suggest that iniA functions through an MDR-pump like mechanism, although IniA does not appear to directly transport INH from the cell. Analysis of two-dimensional crystals of the IniA protein revealed that this predicted transmembrane protein forms multimeric structures containing a central pore, providing further evidence that iniA is a pump component. Our studies elucidate a potentially unique adaptive pathway in mycobacteria. Drugs designed to inhibit the iniA gene product may shorten the time required to treat tuberculosis and may help prevent the clinical emergence of drug resistance

Protein Sequence

>Rv0342, TB.seq 410836:412755 MW:70084 MVPAGLCAYRDLRRKRARKWGDTVTQPDDPRRVGVIVELIDHTIAIAKLNERGDLVQRLTRARQRITDPQVRVVIAGLLK QGKSQLLNSLLNLPAARVGDDEATVVITVVSYSAQPSARLVLAAGPDGTTAAVDIPVDDISTDVRRAPHAGGREVLRVEV GAPSPLLRGGLAFIDTPGVGGLGQPHLSATLGLLPEADAVLVVSDTSQEFTEPEMWFVRQAHQICPVGAVVATKTDLYPR WREIVNANAAHLQRARVPMPIIAVSSLLRSHAVTLNDKELNEESNFPAIVKFLSEQVLSRATERVRAGVLGEIRSATEQL AVSLGSELSVVNDPNLRDRLASDLERRKREAQQAVQQTALWQQVLGDGFNDLTADVDHDLRTRFRTVTEDAERQIDSCDP TAHWAEIGNDVENAIATAVGDNFVWAYQRSEALADDVARSFADAGLDSVLSAELSPHVMGTDFGRLKALGRMESKPLRRG HKMIIGMRGSYGGVVMIGMLSSVVGLGLFNPLSVGAGLILGRMAYKEDKQNRLLRVRSEAKANVRRFVDDISFVVSKQSR DRLKMIQRLLRDHYREIAEEITRSLTESLQATIAAAQVAETERDNRIRELQRQLGILSQVNDNLAGLEPTLTPRASLGRA

Human Homologue Blast Result

Alergen Protein

Link to Algpred
Non Allergen Predicted by AlgPred Server

Bacterial Toxin Prediction

Link to btxpred
No Hit Fountd by btxpred server.

Subcellular Location

Link to TBpred
Cyoplasmic

Antigens

No Hit Found in AntigenDB
No. Hit Found in IEDB

B cell Epitopes

BCEpred Analysis

Link to Bcepred
Result Predicited by [1]

ABCpred Analysis

Link to ABCpred
Result Predicited by [2]

IEDB Analysis

Link to IEDB
Result Predicited by [3]

MHC Class-I Binder

nHLAPred Analysis

Link to nHLApred
Result Predicited by [4]

IEDB Analysis

Link to IEDB
Result Predicted by []

MHC Class-II Binder

Propred Analysis

Link to Propred
Result Predicted by []

NetMHC-II Analysis

Link to NetMHC-II
Result Predicted by []

External Links

• Database of Mycobacterium tuberculosis genome sequences and related information.